Susceptibilidade de populações de Simulium (Chirostilbia pertinax Kollar, 1832 (Culicomorpha, Simuliidae ao temephos e a um formulado à base de Bacillus thuringiensis var. israelensis Susceptibility of population of Simulium (Chirostilbia pertinax Kollar, 1832 (Culicomorpha, Simuliidae to temephos and Bacillus thuringiensis var. israelensis formulation

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Carlos Fernando S. de Andrade

1991-10-01

Full Text Available O uso de pequenas calhas de madeira no leito de riachos, manualmente colonizadas com borrachudos, é proposto para avaliações da eficiência de larvicidas 3 ou 4 horas após as aplicações. A susceptibilidade larval também foi avaliada pelo critério de TL50. Em três ensaios no litoral do Estado de São Paulo e Rio de Janeiro, populações de Simulium (C. pertinax Kollar, 1832 mostraram-se resistentes ao temephos, mesmo em altas concentrações. Vectobac 12 AS, à base de Bacillus thuringiensis var. israelensis mostrou-se mais potente contra larvas dos últimos estádios e eficiente para controle em concentrações a partir de 7.200 UIP/1 (10 min.. O TL50para 3.744 UIP/1 (10 min. foi de 70,9 minutos.The use of wooden troughs on stream beds, artificially colonized by blackfly larvae, is proposed for larvicide evaluations. Mortality was recorded 3 or 4 hours after treatment. Larval susceptibility was also evaluated utilizing the LT50 criterion. In there field assays Simulium (C. pertinax populations from the litoral of S. Paulo and Rio de Janeiro States were shown to be resistant to temephos, even when subjected to high concentrations. Vectobac 12 AS, a Bacillus thuringiensis var. israelensis product, was shown to be more potent against late instar larvae and efficient in concentrations higher than 7,200 ITU/1 (10 min. The LT50 to 3,744 ITU/1 (10 min was calculated as 70.9 min.

Mercury concentration in black flies Simulium spp. (Diptera, Simuliidae) from soft-water streams in Ontario, Canada

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Harding, K.M.; Gowland, J.A.; Dillon, P.J.

2006-01-01

Total Hg in Simulium spp. (Diptera, Simuliidae) was measured in 17 soft-water streams in the District of Muskoka and Haliburton County (Ontario, Canada) during 2003 and 2004. Black flies contained 0.07-0.64 μg/g total Hg (dry weight). The methylmercury concentration was measured in 6 samples of the 17, and ranged from 58% to 93% of total Hg. The concentration of total Hg is much higher than has been found in other filter feeding insects, and represents a significant potential source of Hg to fish. Mercury concentrations in Simulium spp. at different sites were strongly positively correlated with dissolved organic carbon, and the proportion of land within each catchment that was wetland. There was also a strong negative correlation with pH. By examining Hg concentration in filter feeding insects we have found a significant entry point for Hg and MeHg into the food web. - Accumulation of total mercury by black fly larvae is affected by stream pH, DOC and wetland area in the stream catchment

Mercury concentration in black flies Simulium spp. (Diptera, Simuliidae) from soft-water streams in Ontario, Canada

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Harding, K.M. [Trent University, 1600 West Bank Drive, Peterborough, ON K9J 7B8 (Canada); Gowland, J.A. [Trent University, 1600 West Bank Drive, Peterborough, ON K9J 7B8 (Canada); Dillon, P.J. [Trent University, 1600 West Bank Drive, Peterborough, ON K9J 7B8 (Canada)]. E-mail: pdillon@trentu.ca

2006-10-15

Total Hg in Simulium spp. (Diptera, Simuliidae) was measured in 17 soft-water streams in the District of Muskoka and Haliburton County (Ontario, Canada) during 2003 and 2004. Black flies contained 0.07-0.64 {mu}g/g total Hg (dry weight). The methylmercury concentration was measured in 6 samples of the 17, and ranged from 58% to 93% of total Hg. The concentration of total Hg is much higher than has been found in other filter feeding insects, and represents a significant potential source of Hg to fish. Mercury concentrations in Simulium spp. at different sites were strongly positively correlated with dissolved organic carbon, and the proportion of land within each catchment that was wetland. There was also a strong negative correlation with pH. By examining Hg concentration in filter feeding insects we have found a significant entry point for Hg and MeHg into the food web. - Accumulation of total mercury by black fly larvae is affected by stream pH, DOC and wetland area in the stream catchment.

Simulium (Psilopelmia virescens, a new black-fly species (Diptera: Simuliidae from the southwestern region of the state of Bahia, Brazil

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Neusa Hamada

2012-02-01

Full Text Available The last-instar larva, pupa, male and female of Simulium virescens sp. nov. are described and illustrated. This species has a peculiar larva, which has an elongated head capsule and light-green colour. The first thoracic segment has tubercle on its dorsal region and the third thoracic segment has one pair of tubercles; the first to the fourth abdominal segments have one pair of tubercles on each segment. Until now this new species had only been collected at the type locality, which is on the middle stretch of the Correntina River in the southwestern portion of the state of Bahia, Brazil. Females were voraciously biting humans during the field work. This new species represents the second species of Simulium(Psilopelmia in Brazil and the first registered outside of the Brazilian Amazon Region.

Identification of entomopathogenic Bacillus isolated from Simulium (Diptera, Simuliidae larvae and adults

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Cavados CFG

2001-01-01

Full Text Available Entomopathogenic bacteria isolated from Simulium larvae and adults from breeding sites in the states of São Paulo and Rio de Janeiro, Brazil, were identified as 18 strains of Bacillus thuringiensis and one of B. sphaericus. Most of these strains were serotyped according to their flagellar antigens. However, nine of the B. thuringiensis samples, could not be serotyped and were designated as "autoagglutinating"; they were also shown to be toxic in preliminary tests against Aedes aegypti larvae. Additionally, B. sphaericus was also shown to be toxic towards Culex quinquefasciatus larvae.

[Susceptibility of populations of Simulium (Chirostilbia) pertinax Kollar, 1832 (Culicomorpha, Simuliidae) to eemephos and to Bacillus thuringiensis var. israelensis-based formulation].

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de Andrade, C F; Castello Branco Júnior, A

1991-10-01

The use of wooden troughs on stream beds, artificially colonized by blackfly larvae, is proposed for larvicide evaluations. Mortality was recorded 3 or 4 hours after treatment. Larval susceptibility was also evaluated utilizing the LT50 criterion. In there field assays Simulium (C.) pertinax populations from the litoral of S. Paulo and Rio de Janeiro States were shown to be resistant to temephos, even when subjected to high concentrations. Vectobac 12 AS, a Bacillus thuringiensis var. israelensis product, was shown to be more potent against late instar larvae and efficient in concentrations higher than 7,200 ITU/l (10 min). The LT50 to 3,744 ITU/l (10 min) was calculated as 70.9 min.

Cardiocladius oliffi (Diptera: Chironomidae as a potential biological control agent against Simulium squamosum (Diptera: Simuliidae

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Wilson Michael D

2009-04-01

Full Text Available Abstract Background The control of onchocerciasis in the African region is currently based mainly on the mass drug administration of ivermectin. Whilst this has been found to limit morbidity, it does not stop transmission. In the absence of a macrofilaricide, there is a need for an integrated approach for disease management, which includes vector control. Vector control using chemical insecticides is expensive to apply, and therefore the use of other measures such as biological control agents is needed. Immature stages of Simulium squamosum, reared in the laboratory from egg masses collected from the field at Boti Falls and Huhunya (River Pawnpawn in Ghana, were observed to be attacked and fed upon by larvae of the chironomid Cardiocladius oliffi Freeman, 1956 (Diptera: Chironomidae. Methods Cardiocladius oliffi was successfully reared in the rearing system developed for S. damnosum s.l. and evaluated for its importance as a biological control agent in the laboratory. Results Even at a ratio of one C. oliffi to five S. squamosum, they caused a significant decrease in the number of adult S. squamosum emerging from the systems (treatments. Predation was confirmed by the amplification of Simulium DNA from C. oliffi observed to have fed on S. squamosum pupae. The study also established that the chironomid flies could successfully complete their development on a fish food diet only. Conclusion Cardiocladius oliffi has been demonstrated as potential biological control agent against S. squamosum.

Cryptic Biodiversity and the Origins of Pest Status Revealed in the Macrogenome of Simulium colombaschense (Diptera: Simuliidae, History's Most Destructive Black Fly.

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Peter H Adler

Full Text Available The European black fly Simulium (Simulium colombaschense (Scopoli, once responsible for as many as 22,000 livestock deaths per year, is chromosomally mapped, permitting its evolutionary relationships and pest drivers to be inferred. The species is 12 fixed inversions removed from the standard sequence of the subgenus Simulium. Three of these fixed inversions, 38 autosomal polymorphisms, and a complex set of 12 X and 6 Y chromosomes in 29 zygotic combinations uniquely characterize S. colombaschense and reveal 5 cytoforms: 'A' in the Danube watershed, 'B' in Italy's Adige River, 'C' in the Aliakmonas River of Greece, 'D' in the Aoös drainage in Greece, and 'E' in the Belá River of Slovakia. 'C' and 'D' are reproductively isolated from one another, and 'B' is considered a cytotype of 'A,' the probable name bearer of colombaschense. The species status of 'E' cannot be determined without additional collections. Three derived polytene sequences, based on outgroup comparisons, place S. colombaschense in a clade of species composed of the S. jenningsi, S. malyschevi, and S. reptans species groups. Only cytoforms 'A' and 'B' are pests. Within the Simuliidae, pest status is reached through one of two principal pathways, both of which promote the production of large populations of blood-seeking flies: (1 colonization of the world's largest rivers (habitat specialization or (2 colonization of multiple habitat types (habitat generalization. Evolutionary acquisition of the ability to colonize large rivers by an ancestor of the S. jenningsi-malyschevi-reptans clade set the scene for the pest status of S. colombaschense and other big-river members of the clade. In an ironic twist, the macrogenome of S. colombaschense reveals that the name associated with history's worst simuliid pest represents a complex of species, two or more of which are nonpests potentially vulnerable to loss of their limited habitat.

Molecular identification of infective larvae of three species of Onchocerca found in wild-caught females of Simulium bidentatum in Japan

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Fukuda M.

2010-03-01

Full Text Available Wild female black flies attracted to a man or an idling automobile were collected at Oita, Japan where five cases of zoonotic onchocerciasis had occurred. Among the five Simulium species captured, 2% of Simulium bidentatum, the predominant species, were infected with filarial larvae. There were at least two types of infective larvae, types A and B, based on morphometric observation. Moreover, molecular analysis of the mitochondrial cytochrome c oxidase subunit 1 (CO1 gene revealed that types A and B were represented by a single unknown species of Onchocerca and two species, i.e., Onchocerca dewittei japonica from wild boar, the causative agent of zoonotic onchocerciasis in Japan, and an undescribed Onchocerca sp. from wild boar, respectively. Phylogenetic analysis based on the sequences of the mitochondrial 12S ribosomal RNA (12S rRNA gene also showed that type A is likely to be an unknown species of Onchocerca. Natural infection of black flies with infective larvae of O. dewittei japonica and O. sp. was demonstrated for the first time. The present study strongly suggests that S. bidentatum plays a role as a vector in the transmission of zoonotic onchocerciasis due to O. dewittei japonica in Japan.

Development of a Novel Trap for the Collection of Black Flies of the Simulium ochraceum Complex

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Rodríguez-Pérez, Mario A.; Adeleke, Monsuru A.; Burkett-Cadena, Nathan D.; Garza-Hernández, Javier A.; Reyes-Villanueva, Filiberto; Cupp, Eddie W.; Toé, Laurent; Salinas-Carmona, Mario C.; Rodríguez-Ramírez, Américo D.; Katholi, Charles R.; Unnasch, Thomas R.

2013-01-01

Background Human landing collections are currently the standard method for collecting onchocerciasis vectors in Africa and Latin America. As part of the efforts to develop a trap to replace human landing collections for the monitoring and surveillance of onchocerciasis transmission, comprehensive evaluations of several trap types were conducted to assess their ability to collect Simulium ochraceum sensu lato, one of the principal vectors of Onchocerca volvulus in Latin America. Methodology/Principal Findings Diverse trap designs with numerous modifications and bait variations were evaluated for their abilities to collect S. Ochraceum s.l. females. These traps targeted mostly host seeking flies. A novel trap dubbed the “Esperanza window trap” showed particular promise over other designs. When baited with CO2 and BG-lure (a synthetic blend of human odor components) a pair of Esperanza window traps collected numbers of S. Ochraceum s.l. females similar to those collected by a team of vector collectors. Conclusions/Significance The Esperanza window trap, when baited with chemical lures and CO2 can be used to collect epidemiologically significant numbers of Simulium ochraceum s.l., potentially serving as a replacement for human landing collections for evaluation of the transmission of O. volvulus. PMID:24116169

On the ecology of the fauna of stones in the current in a South African river supporting a very large simulium (Diptera) population

CSIR Research Space (South Africa)

Chutter, FM

1968-12-01

Full Text Available the studies described here were made. The first aim of this work was to record the density of the Simulium larvae and also of the other invertebrate animals in the river at different times of the year from Warrenton down to Barkly West....

Using trap crops for control of Acalymma vittatum (Coleoptera: Chrysomelidae) reduces insecticide use in butternut squash.

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Cavanagh, A; Hazzard, R; Adler, L S; Boucher, J

2009-06-01

Striped cucumber beetle, Acalymma vittatum F., is the primary insect pest of cucurbit crops in the northeastern United States. Adult beetles colonize squash crops from field borders, causing feeding damage at the seedling stage and transmitting bacterial wilt Erwinia tracheiphila Hauben et al. 1999. Conventional control methods rely on insecticide applications to the entire field, but surrounding main crops with a more attractive perimeter could reduce reliance on insecticides. A. cittatum shows a marked preference for Blue Hubbard squash (Cucurbita maxima Duchesne) over butternut squash (C. moschata Poir). Given this preference, Blue Hubbard squash has the potential to be an effective perimeter trap crop. We evaluated this system in commercial butternut fields in 2003 and 2004, comparing fields using perimeter trap cropping with Blue Hubbard to conventionally managed fields. In 2003, we used a foliar insecticide to control beetles in the trap crop borders, and in 2004, we compared systemic and foliar insecticide treatments for the trap crop borders. We found that using a trap crop system reduced or eliminated the need to spray the main crop area, reducing insecticide use by up to 94% compared with conventional control methods, with no increase in herbivory or beetle numbers. We surveyed the growers who participated in these experiments and found a high level of satisfaction with the effectiveness and simplicity of the system. These results suggest that this method of pest control is both effective and simple enough in its implementation to have high potential for adoption among growers.

New molecular identifiers for Simulium limbatum and Simulium incrustatum s.l. and the detection of genetic substructure with potential implications for onchocerciasis epidemiology in the Amazonia focus of Brazil.

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Conceição, Priscila A; Crainey, James L; Almeida, Tatiana P; Shelley, Anthony J; Luz, Sergio L B

2013-08-01

The Amazonia onchocerciasis focus of southern Venezuela and northern Brazil is the larger of the two remaining Latin American onchocerciasis foci where disease transmission still occurs and is often regarded as the most challenging of all the Latin American foci to eliminate onchocerciasis. The site is home to a population of over 20,000 semi-nomadic, hunter-gatherer Yanomami people and is made-up of a mosaic of rainforest and savannah ecologies, which are influenced by the area's undulating terrain and rich geological diversity. At least six blackfly vectors have been implicated in onchocerciasis transmission in this focus; however, because of the difficulty in their routine identification the relative importance of each has been obscured. Simulium limbatum and Simulium incrustatum s.l. have both been recorded as vectors in the Amazonia focus, but they are difficult to discriminate morphologically and thus the ecological range of these species, and indeed the presence of S. limbatum in the Amazonia focus at all, have remained controversial. In the work described here, we report 15 S. incrustatum s.l. CO1 sequences and 27 S. limbatum sequences obtained from field-caught adult female blackflies collected from forest and savannah localities, inside and just outside the Amazonia focus. Phylogenetic analysis with the sequences generated in this study, showed that both the S. limbatum and the S. incrustatum s.l. CO1 sequences obtained (even from specimens living in sympatry) all fell into discrete species-specific bootstrap-supported monophyletic groups and thus confirmed the utility of the CO1 gene for identifying both these species inside the Amazonia focus. As the S. limbatum-exclusive cluster included CO1 sequences obtained from forest-caught and morphologically identified specimens these results provide the clearest evidence yet of the presence of S. limbatum inside the Amazonia focus. The question, however, of whether S. limbatum is actually a vector in the focus

Infective larvae of five Onchocerca species from experimentally infected Simulium species in an area of zoonotic onchocerciasis in Japan

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Fukuda M.

2008-06-01

Full Text Available Microfilariae of five Onchocerca species, O. dewittei japonica (the causative agent of zoonotic onchocerciasis in Oita, Kyushu, Japan from wild boar (Sus scrofa, O. skrjabini and O. eberhardi from sika deer (Cervus nippon, O. lienalis from cattle, and an as yet unnamed Onchocerca sp. from wild boar, were injected intrathoracically into newly-emerged black flies of several species from Oita to search the potential vector(s of these parasites and identify their infective larvae. Development of O. dewittei japonica microfilariae to the infective larvae occurred in Simulium aokii, S. arakawae, S. bidentatum, S. japonicum, S. quinquestriatum, and S. rufibasis while development of infective larvae of O. skrjabini, O. eberhardi, and the unnamed Onchocerca sp. was observed in S. aokii, S. arakawae, and S. bidentatum. Development of O. lienalis microfilaria to infective larvae occurred in S. arakawae. Based on the morphology of infective larvae obtained, we proposed a key of identification of Onchocerca infective larvae found in Oita. We also reconsider the identification of three types of infective larvae previously recovered from Simulium species captured at cattle sheds: the large type I larvae that may be an undescribed species; the small type III identified as O. lienalis may include O. skrjabini too; the intermediary type II that may be O. gutturosa, or O. dewittei japonica, or the unnamed Onchocerca sp. of wild boar.

Evidence of phenotypic plasticity of larvae of Simulium subpallidum Lutz in different streams from the Brazilian Cerrado

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Ronaldo Figueiró

2015-03-01

Full Text Available In this paper, the overall morphological differences between populations of Simulium subpallidum Lutz, 1909 are studied. Several studies found in the literature point to a relationship between the labral fans and body size and the habitat where blackfly larvae occur. However, other characteristics potentially related to the microhabitat, such as abdominal hook circlet morphology, which is used for larvae to fix themselves in the substratum, and thoracic prolegs morphology, which help larvae move in the substratum, were analyzed in three different populations of S. subpallidum, one of which occupied a faster flow. The results suggest phenotypic plasticity in S. subpallidum and a tendency toward larger structures in faster flows.

Phylogeography and population diversity of Simulium hirtipupa Lutz (Diptera: Simuliidae based on mitochondrial COI sequences.

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Vanderly Andrade-Souza

Full Text Available High morphological homogeneity and cryptic speciation may cause the diversity within Simuliidae to be underestimated. Recent molecular studies on population genetics and phylogeography have contributed to reveal which factors influenced the diversity within this group. This study aimed at examining the genetic diversity of Simulium hirtipupa Lutz, 1910 in populations from the biomes Caatinga, Cerrado, and Atlantic Forest. In this study, we carried out phylogeographic and population genetic analyses using a fragment of the mitochondrial gene COI. The 19 populations studied were clustered into seven groups, most of which are associated with geography indicating certain genetic structure. The northern region of the state of Minas Gerais is most likely the center of origin of this species. The average intergroup genetic distance was 3.7%, indicating the presence of cryptic species. The species tree as well as the haplotype network recovered all groups forming two major groups: the first comprises groups Gr-Bahia (in which the São Francisco river has not acted as geographical barrier, Gr-Pernambuco, and Gr-Mato Grosso do Sul. The second included groups comprising populations of the states of Goiás, Tocantins, Minas Gerais, Bahia, São Paulo, and Espírito Santo. The mismatch distribution for groups was consistent with the model of demographic expansion, except for the Gr-Central-East_1 group. The diversification in this group occurred about 1.19 Mya during the Pleistocene, influenced by paleoclimatic oscillations during the Quaternary glacial cycles.

Cues used by the black fly, Simulium annulus, for attraction to the common loon (Gavia immer).

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Weinandt, Meggin L; Meyer, Michael; Strand, Mac; Lindsay, Alec R

2012-12-01

The parasitic relationship between a black fly, Simulium annulus, and the common loon (Gavia immer) has been considered one of the most exclusive relationships between any host species and a black fly species. To test the host specificity of this blood-feeding insect, we made a series of bird decoy presentations to black flies on loon-inhabited lakes in northern Wisconsin, U.S.A. To examine the importance of chemical and visual cues for black fly detection of and attraction to hosts, we made decoy presentations with and without chemical cues. Flies attracted to the decoys were collected, identified to species, and quantified. Results showed that S. annulus had a strong preference for common loon visual and chemical cues, although visual cues from Canada geese (Branta canadensis) and mallards (Anas platyrynchos) did attract some flies in significantly smaller numbers. © 2012 The Society for Vector Ecology.

Simulium (Psaroniocompsa tergospinosum new species (Diptera: Simuliidae in siolii group from the southern part of the State of Amazonas, Brazil

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Neusa Hamada

2000-12-01

Full Text Available The larva, pupa, male and female of Simulium tergospinosum n. sp. are described and illustrated. The adults of this new species share many characters with species in the subgenus Psaroniocompsa, where it is placed. The larva of this species bears dorsal and lateral triangular tubercles on the abdomen and multiply branched scale-like setae on the body, suggesting that it belongs to the S. siolii species group. S. tergospinosum n.sp. was collected along the Juma River, Apuí county, in the southern part of the State of Amazonas, Brazil. The Juma, a black-water river, is a tributary of the Aripuanã River in the Madeira River hydrographic basin, on the southern part of Amazonas. Females were collected biting humans along the water courses during the sampling period (in the dry season.

Blackflies (Diptera: Simuliidae) in Croatia: species richness, distribution and relationship to surrounding countries.

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Ivković, Marija; Kúdela, Matuš; Kúdelová, Tatiana

2016-05-05

All records of blackflies (Simuliidae) from the territory of Croatia are summarized, including previously unpublished data. The blackfly fauna of Croatia consists of 28 species. Simulium (Nevermannia) angustitarse (Lundström), Simulium (Nevermannia) cryophilum (Rubtsov) complex, Simulium (Nevermannia) lundstromi (Enderlein), Simulium (Nevermannia) vernum Macquart complex, Simulium (Simulium) argyreatum Meigen, Simulium (Simulium) bezzii (Corti) complex, Simulium paraequinum Puri and Simulium pseudequinum Séguy are reported for the first time from Croatia. Information related to the ecoregions, in which species were found and specific species traits are given. Genus Prosimulium Roubaud is represented by one species only. Genus Simulium Latreille is represented by 27 species in six subgenera, with subgenus Simulium Latreille s. str. being most species rich (13 species) and subgenera Boophthora Enderlein and  Trichodagmia Enderlein represented each by only one species. Compared to the neighboring countries, the Croatian species assemblage is most similar to the fauna of Slovenia and least similar to that of Italy. The relatively low number of species, presence of several species complexes and unclear identity of other species show that further research of blackflies in Croatia is needed.

Determining the Number of Instars in Simulium quinquestriatum (Diptera: Simuliidae) Using k-Means Clustering via the Canberra Distance.

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Yang, Yao Ming; Jia, Ruo; Xun, Hui; Yang, Jie; Chen, Qiang; Zeng, Xiang Guang; Yang, Ming

2018-02-21

Simulium quinquestriatum Shiraki (Diptera: Simuliidae), a human-biting fly that is distributed widely across Asia, is a vector for multiple pathogens. However, the larval development of this species is poorly understood. In this study, we determined the number of instars in this pest using three batches of field-collected larvae from Guiyang, Guizhou, China. The postgenal length, head capsule width, mandibular phragma length, and body length of 773 individuals were measured, and k-means clustering was used for instar grouping. Four distance measures-Manhattan, Euclidean, Chebyshev, and Canberra-were determined. The reported instar numbers, ranging from 4 to 11, were set as initial cluster centers for k-means clustering. The Canberra distance yielded reliable instar grouping, which was consistent with the first instar, as characterized by egg bursters and prepupae with dark histoblasts. Females and males of the last cluster of larvae were identified using Feulgen-stained gonads. Morphometric differences between the two sexes were not significant. Validation was performed using the Brooks-Dyar and Crosby rules, revealing that the larval stage of S. quinquestriatum is composed of eight instars.

Aspectos ecológicos de Simulium goeldii (Diptera: Simuliidae: relação entre substrato e densidade de larvas Ecological aspects of Simulium goeldii (Diptera: Simuliidae: relation between substrate and larval density

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Neusa Hamada

1989-01-01

Full Text Available The distribution of larvae of Simulium goeldii was studies in four streams in upland tropical forest near Manaus, Amazonas, Brazil. In each month 32 points were sampled, each with an area of 30 x 50 cm. The areas of all substrates available were measured at each point. The larvae of S. goeldii were collected and later counted for all substrate types where larvae of this species were found. The available substrates were classified into eight types: dry leaves, green leaves, branches, fruits, detritus, rocks and sand; anly the first four types had larvae present. The Kruskal-Wallis test and analysis of variance indicated that the larvae occupy these substrates differently; the Newman-Keuls identified the following differences in intensity of occupation of the susbstrates: branchs differ from roots, dry leaves and green leaves, and green leaves differ from roots and dry leaves. The highest density of larvae was observed on green leaves. However, because the most abundant substrates in the study area were roots and dry leaves, I suggest that the latter two substrates are the most important ones for the esteblishment of this population of S. goeldii.

Fauna of Simuliidae (Diptera from the state of Espírito Santo, Brazil: distribution, new records and list of species

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Karina Bertazo

2013-03-01

Full Text Available Fauna of Simuliidae (Diptera from the state of Espírito Santo, Brazil: Distribution, new records and list of species. The fauna of Simuliidae in Brazil is composed of 87 species, 17 of which are recorded from the state of Espírito Santo. Entomological collections were carried out in 2010-2011 with the objective of increasing the knowledge of the species richness of this family in the state. Ninety three rivers and streams were sampled, each collection being carried out in a 50m transect. During the study period 30 species were collected, 13 of which represent new records for the state, 12 of the genus Simulium and one of the genus Lutzsimulium. Among these new state records one, Simulium lobatoi, also represents a new record from southeastern Brazil. The other newly recorded species are: Lutzsimulium hirticosta, Simulium distinctum, Simulium exiguum, Simulium oyapockense, Simulium botulibranchium, Simulium petropoliense, Simulium clavibranchium, Simulium rappae, Simulium minusculum, Simulium dinellii, Simulium ochraceum and Simulium scutistriatum.

NCBI nr-aa BLAST: CBRC-TBEL-01-1221 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-TBEL-01-1221 ref|YP_635917.1| cell division protein [Helicosporidium sp. ex Simulium jones...ii] sp|Q2EEX7|FTSH_HELSJ Cell division protease ftsH homolog gb|ABD33966.1| ftsH protease [Helicosporidium sp. ex Simulium jonesii] YP_635917.1 3.4 24% ...

Comments on the association of immatures of Hemerodromia (Diptera, Empididae) and Simulium (Diptera, Simuliidae), and first record of this association in the Atlantic Forest (Brazil).

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Sánchez Molina, Óscar; Gil-Azevedo, Leonardo Henrique

2016-11-01

Larvae of Empididae (Diptera) prey on black fly immatures and its pupae can be collected from pupal cases of Simuliidae (Diptera). The aim of our work was to report the second record of association between immatures of Empididae and Simuliidae in the Neotropical Region and the first for the Atlantic Forest (Rio de Janeiro, Brazil). We collected 4982 pupae and exuviae of Simulium Latreille, (Diptera, Simuliidae) and found three with a pupa of Hemerodromia Meigen (Diptera, Empididae) inside. This shows that the use of black flies cocoons by dance flies occurs at extremely low frequencies, which might explain why this association is so rarely recorded. Our results are relevant for a better comprehension of the predator-prey relationship between these families. Copyright © 2016 Elsevier B.V. All rights reserved.

Larval biometry of Simulium rubrithorax (Diptera: Simuliidae and size comparison between populations in the states of Minas Gerais and Roraima, Brazil

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Alvan-Aguilar Miriam Adriana

2003-01-01

Full Text Available The number of larval instars of Simulium (Hemicnetha rubrithorax Lutz (Diptera: Nematocera was determined using the lateral length of the head capsule. In this study 1,035 larvae, of different sizes, were measured (639 from the state of Roraima and 396 from the state of Minas Gerais. A frequency distribution analysis was carried out on the measurements of the lateral length of the head capsule to determine the number of larval instars. The limits of each instar were defined by the lower frequency of the measurements falling in a range of values, by the presence of the "egg burster" that characterizes the first larval instar, and by the developmental stage of the gill histoblast. The determination of the instar number was tested using a Student's t-test (p 0.05 were observed between them.

Diurnal biting periodicity of parous Simulium (Diptera: Simuliidae) vectors in the onchocerciasis Amazonian focus.

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Grillet, M-E; Villamizar, N J; Cortez, J; Frontado, H L; Escalona, M; Vivas-Martínez, S; Basáñez, M-G

2005-05-01

We describe the hourly patterns of parous biting activity of the three main simuliid vectors of human onchocerciasis in the Amazonian focus straddling between Venezuela and Brazil, namely, Simulium guianense s.l. Wise; S. incrustatum Lutz, and S. oyapockense s.l. Floch and Abonnenc. Time series of the hourly numbers of host-seeking parous flies caught in five Yanomami villages during dry, rainy, and their transition periods from 1995 to 2001 were investigated using harmonic analysis (assuming an underlying circadian rhythm) and periodic correlation (based on Spearman's r). Parous S guianense s.l. showed a bimodal activity pattern, with a minor peak in mid-morning and a major peak at 16:00 h. S. incrustatum exhibited mainly unimodal activity during either early morning or midday according to locality. S. oyapockense s.l. bit humans throughout the day mainly between 10:00 and 16:00 h but also showed bimodal periodicity in some localities. Superimposed on the endogenous, species-specific daily cycles, parous activity showed variation according to locality, season, air temperature and relative humidity, with biting being promoted by warmer and drier hours during wet seasons/periods and reduced during hotter times in dry seasons or transitions. The results are discussed in terms of their implications for blackfly biology and ecology as well as onchocerciasis epidemiology and control.

A new simple technique for rearing F1 progeny from females of the Simulium damnosum Theobald complex.

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Raybould, J N; Barro, T; Sawadogo, R; Mordzifa, F

1982-06-01

Laboratory rearing of Simulium damnosum complex species enables female adults to be indirectly identified from their larval progeny. A simple, readily transportable rearing apparatus was developed for investigations by the Onchocerciasis Control programme by using unbreakable, easily packed and reassembled parts and by feeding the larvae at least partly with living green algae (Chlorophyceae) cultured in the laboratory. Although the larvae are sensitive to excess nitrogen compounds, the use of algae and a large volume of water obviated the need for a separate purification system in which water was circulated by an A/C electrical centrifugal pump between a container and an inclined trough in which most of the larvae developed. The rate of development was rapid giving rise to full size larvae (suitable for cytotaxonomic determination), pupae and adults. The adults were attracted into a collecting device by light. Developments to protect the larvae during electrical power failures included a slow-drying wooden rearing trough and an automatic switch to an alternative D/C power supply and pump. This technique has been in general use in O.C.P. laboratories in Benin, Ghana, Ivory Coast and Upper Volta and many thousands of larvae have been reared.

The Potential for Dispersal of Onchocerciasis in Ecuador in Relation to the Distribution of the Vector Simulium exiguum (Diptera:Simuliidae

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Charalambous M

1997-01-01

Full Text Available The future dispersal of onchocerciasis in Ecuador is dependent on the distribution of cytotypes of the vector species complex Simulium exiguum. Over the last 14 years, collections of larvae have been made from over 25 rivers, between 80-1600 m altitude, from various sites on both sides of the Andes. Analysis of larval polytene chromosomes was used to determine the distributions of each cytotype. On the western side of the Andes, the Cayapa cytotype (the only cytotype directly incriminated as a vector has a distribution from Santo Domingo de los Colorados northwards. The Quevedo and Bucay cytotypes occur from Santo Domingo de los Colorados southwards. On the eastern side of the Andes, the Aguarico cytotype occurs in the Rio Aguarico and a new cytotype is present in the tributaries of the Rio Napo. Whether the disease will spread south of Santo Domingo and on the eastern side of the Andes depends on vector capacity of the cytotypes and the dispersal patterns of individuals infected with onchocerciasis. At present the Aguarico, Bucay and Quevedo cytotypes are known to be efficient hosts, but their biting preferences and biting densities have not yet been evaluated

Cytological and isoenzyme analysis of the Bucay and Quevedo cytotypes of the onchocerciasis vector Simulium exiguum (Diptera: Simuliidae in Ecuador

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M. Charalambous

1993-03-01

Full Text Available Four cytotypes of Simulium exiguum occur in Ecuador, where this morphospecies is the primary vector of onchocerciasis. In this paper, we give the first full description of the banding pattern of the larval polytene chromosomes of the Quevedo cytotypes differ from the chromosomal standard sequence (of the Cayapa cytotype by the fixed inversions IIL-5 and IIL-6. The Quevedo cytotype additionally differs from the standard and Bucay cytotypes by processing a differentiated X chromosome, wich is indicated by the inversion IIS-A. As the degree of reproductive isolation between the Bucay and Quevedo cytotypes has not yet been estabilished, they must be regarded as intraspecific variants of the same species. In fact, isoenzyme characterizations showed that the Bucay and Quevedo cytotypes are differentiated only to the extent expected of incipient species or geographical populations. Moreover, the sibiling species status previously given to the Bucay cytotype needs be reassessed, there being inadequate analysis from areas in Ecuador where Bucay occurs in sympatry with the standard Cayapa cytotype. No isoenzyme electromorphs were discovered that identified all or mostadult females of any one (cytotype-pure collection.

Seasonal and diurnal biting activities and zoonotic filarial infections of two Simulium species (Diptera: Simuliidae in northern Thailand

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Ishii Y.

2008-06-01

Full Text Available Seasonal and daily biting activity patterns, and natural filarial infections of adult black flies attracted to human bait were investigated at Ban Pang Faen, a rural area in Chiang Mai Province in northern Thailand. Collections were carried out twice a month from 06-00 to 18-00 hours from January 2005 to February 2006. Among ten Simulium species collected, S. nodosum and S. asakoae were predominant occupying 57.3% and 37.2% of the total 16, 553 females, respectively. These two predominant species showed different patterns in seasonal abundance: majority of S. nodosum (86.7% were collected in hot season (from mid February to mid May, while most of S. asakoae (74.5% were collected in rainy season (from mid May to mid October. For the daily biting activity, S. nodosum had two patterns: the main one was unimodal with a peak from 17-00 to 18-00, and the other was bimodal and had the major peak from 16-00 to 18-00 and the minor one from 07-00 to 09-00. The pattern of S. asakoae was mostly unimodal with a peak from 06-00 to 10-00. The filarial larvae found in S. nodosum and S. asakoae were morphologically different from each other. The short and thick infective larvae found in S. asakoae differed from all known filarial larvae; it is suggested that they might be a bird parasite, Splendidofilariinae or Lemdaninae. The infection of the mammophilic S. nodosum with large Onchocerca type infective larvae was confirmed in this area. Natural filarial infections were found in each month (except December in either S. nodosum or S. asakoae or in both. Monthly infection rates with all stages of larvae were 0.6-5.0% for S. nodosum, and 1.0-4.0% for S. asakoae. It is suggested that people in this village are exposed to the risk of infection with zoonotic filariae throughout the year.

Checklist of the family Simuliidae (Diptera of Finland

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Jari Ilmonen

2014-09-01

Full Text Available A checklist of the family Simuliidae (Diptera is provided for Finland and recognizes 56 species. One new record has been added (Simulium latipes and one name sunken in synonymy (Simulium carpathicum. Furthermore, Simulium tsheburovae is treated as a doubtful record.

Histopathological and ultrastructural effects of delta-endotoxins of Bacillus thuringiensis serovar israelensis in the midgut of Simulium pertinax larvae (Diptera, Simuliidae

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CFG Cavados

2004-08-01

Full Text Available The bacterium Bacillus thuringiensis (Bt produces parasporal crystals containing delta-endotoxins responsible for selective insecticidal activity on larvae. Upon ingestion, these crystals are solubilized in the midgut lumen and converted into active toxins that bind to receptors present on the microvilli causing serious damage to the epithelial columnar cells. We investigated the effect of these endotoxins on larvae of the Simulium pertinax, a common black fly in Brazil, using several concentrations during 4 h of the serovar israelensis strain IPS-82 (LFB-FIOCRUZ 584, serotype H-14 type strain of the Institute Pasteur, Paris. Light and electron microscope observations revealed, by time and endotoxin concentration, increasing damages of the larvae midgut epithelium. The most characteristic effects were midgut columnar cell vacuolization, microvilli damages, epithelium cell contents passing into the midgut lumen and finally the cell death. This article is the first report of the histopathological effects of the Bti endotoxins in the midgut of S. pertinax larvae and the data obtained may contribute to a better understanding of the mode of action of this bacterial strain used as bioinsecticide against black fly larvae.

Efectos de la dispersión sobre la reconstrucción por árboles reconciliados y el patrón de distribución de los subgéneros neotropicales de Simulium (Diptera:Simuliidae

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Miranda-Esquivel Daniel Rafael

2001-07-01

Full Text Available The analysis ofthe distribution pattern ofNeotropical Simulium (Diptera:Simuliidae subgenera suggests that dispersal between Mesoamerica and the Pacifíc region, and SE of Brazil and Cerrado could interfere with the evaluation of the general pattern. To agree with the premise ofno dispersion when reconciliated trees is used and to tackle the dispersal problem, the most frequent events of dispersal to each subgenus were eliminated. The dispersal evaluation was carried out using the dispersal-vicariance approach. Reconciliated trees approach, optimizing losses, yields six cladograms and the strict consensus is congruent with previous works using terrestrial organisms where there are two domains: Neotropics and antarctic.El análisis de los patrones biogeográficos de los subgéneros neotropicales de Simulium (Diptera:Simuliidae, sugiere que los eventos de dispersión desde Mesoamerica a la región Pacífica y del SE de Brasil al Cerrado pueden oscurecer la reconstrucción del patrón de las áreas. Para ser concordantes con este fenómeno y  con las limitantes del método de árboles reconciliados, que supone no dispersión, se evaluó los eventos de dispersión para cada subgénero usando el enfoque de dispersión-vicarianza y los eventos de dispersión más frecuentes fueron eliminados de la reconstrucción al usar árboles reconciliados. Al optimizar el número de perdidas se obtienen seis cladogramas de áreas; el consenso estricto sugiere relaciones entre áreas que son congruentes con estudios biogeográficos preliminares usando organismos terrestres donde se presentan claramente los dominios antártico y neotropical. 

Seasonal biodiversity of black flies (Diptera: Simuliidae) and evaluation of ecological factors influencing species distribution at Doi Pha Hom Pok National Park, Thailand.

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Srisuka, Wichai; Takaoka, Hiroyuki; Otsuka, Yasushi; Fukuda, Masako; Thongsahuan, Sorawat; Taai, Kritsana; Choochote, Wej; Saeung, Atiporn

2015-09-01

This is the first study on the seasonal biodiversity of black flies and evaluation of ecological factors influencing their distribution at Doi Pha Hom Pok National Park, northern Thailand. Larvae were collected from six fixed-stream sites in relation to altitude gradients from May 2011 to April 2013. The water temperature, water pH, conductivity, total dissolved solids (TDS), salt, water velocity, stream width and depth, streambed particle sizes, riparian vegetation, and canopy cover were recorded from each site. Monthly collections from the six sites yielded 5475 last-instar larvae, belonging to 29 black fly species. The most frequently found species from all sites were Simulium asakoae (100%) followed by Simulium yuphae (83.3%), and Simulium chiangdaoense, Simulium gombakense, Simulium phahompokense, Simulium fruticosum, Simulium maeaiense and Simulium fenestratum (66.6%). Of the 5475 last-instar larvae, S. maeaiense (19.3%), S. chiangdaoense (15.8%) and S. asakoae (14.8%), were the three most abundant species. The Shannon diversity index (H) at the six sites with different altitudes of 2100m, 2000m, 1500m, 1400m, 700m, and 500m above mean sea level, were 2.042, 1.832, 2.158, 2.123, 1.821 and 1.822, respectively. The Shannon index and number of taxa in the cold season were higher than those in the rainy and hot seasons. Principal component analysis (PCA) indicated that at least three principal components have eigen values >1.0 and accounted for 93.5% of the total variability of ecological factors among sampling sites. The Canonical correspondence analyses (CCA) showed that most species had a trend towards altitude, canopy cover, riparian vegetation and water velocity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Mitochondrial DNA markers reveal high genetic diversity but low genetic differentiation in the black fly Simulium tani Takaoka & Davies along an elevational gradient in Malaysia.

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Van Lun Low

Full Text Available The population genetic structure of Simulium tani was inferred from mitochondria-encoded sequences of cytochrome c oxidase subunits I (COI and II (COII along an elevational gradient in Cameron Highlands, Malaysia. A statistical parsimony network of 71 individuals revealed 71 haplotypes in the COI gene and 43 haplotypes in the COII gene; the concatenated sequences of the COI and COII genes revealed 71 haplotypes. High levels of genetic diversity but low levels of genetic differentiation were observed among populations of S. tani at five elevations. The degree of genetic diversity, however, was not in accordance with an altitudinal gradient, and a Mantel test indicated that elevation did not have a limiting effect on gene flow. No ancestral haplotype of S. tani was found among the populations. Pupae with unique structural characters at the highest elevation showed a tendency to form their own haplotype cluster, as revealed by the COII gene. Tajima's D, Fu's Fs, and mismatch distribution tests revealed population expansion of S. tani in Cameron Highlands. A strong correlation was found between nucleotide diversity and the levels of dissolved oxygen in the streams where S. tani was collected.

Morphometric comparison of Simulium perflavum larvae (Diptera: Simuliidae in relation to season and gender in Central Amazônia, Brazil

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Yamile B Alencar

2001-08-01

Full Text Available Number of larval instars, age structure and environmental effects on these parameters represent basic information in the study of insect population biology. When species have economic importance, this information is essential in order to choose the best period to apply different control methods and to determine the stages of the life cycle of the insect that are most susceptible to each treatment. The family Simuliidae has many species of medical/veterinary importance in the world, and some studies in the temperate region have suggested that the number of larval instars and the larval size can vary according to the season, gender and some environmental factors, such as temperature and diet. This study, with the zoophilic species Simulium perflavum Roubaud, is the first in the Neotropics observing some of these factors and will serve as a template for other species of medical importance in the region. S. perflavum larvae were collected in five streams in Central Amazônia (Manaus and Presidente Figueiredo counties, State of Amazonas, in Sept./Oct. 1996 (dry season and Feb./Mar. 1997 (rainy season. These larvae were measured (lateral length of head capsule and width of cephalic apodema to determine the number of larval instars (n=3985, to compare the larval size between seasons and genders (last and penultimate larval instars, n=200. Seven larval instars were determined for this species using frequency distributions, t-tests and Crosby´s growth rule. Significant differences were not detected (t-test, p>0.05 in larval size between seasons and genders. Our results differ from some found in temperate regions suggesting that in the Neotropical region the larval size in different seasons and different genders remains constant, although some environmental parameters, such as diet, change depending on the season.

The Genomic Architecture of Novel Simulium damnosum Wolbachia Prophage Sequence Elements and Implications for Onchocerciasis Epidemiology

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James L. Crainey

2017-05-01

Full Text Available Research interest in Wolbachia is growing as new discoveries and technical advancements reveal the public health importance of both naturally occurring and artificial infections. Improved understanding of the Wolbachia bacteriophages (WOs WOcauB2 and WOcauB3 [belonging to a sub-group of four WOs encoding serine recombinases group 1 (sr1WOs], has enhanced the prospect of novel tools for the genetic manipulation of Wolbachia. The basic biology of sr1WOs, including host range and mode of genomic integration is, however, still poorly understood. Very few sr1WOs have been described, with two such elements putatively resulting from integrations at the same Wolbachia genome loci, about 2 kb downstream from the FtsZ cell-division gene. Here, we characterize the DNA sequence flanking the FtsZ gene of wDam, a genetically distinct line of Wolbachia isolated from the West African onchocerciasis vector Simulium squamosum E. Using Roche 454 shot-gun and Sanger sequencing, we have resolved >32 kb of WO prophage sequence into three contigs representing three distinct prophage elements. Spanning ≥36 distinct WO open reading frame gene sequences, these prophage elements correspond roughly to three different WO modules: a serine recombinase and replication module (sr1RRM, a head and base-plate module and a tail module. The sr1RRM module contains replication genes and a Holliday junction recombinase and is unique to the sr1 group WOs. In the extreme terminal of the tail module there is a SpvB protein homolog—believed to have insecticidal properties and proposed to have a role in how Wolbachia parasitize their insect hosts. We propose that these wDam prophage modules all derive from a single WO genome, which we have named here sr1WOdamA1. The best-match database sequence for all of our sr1WOdamA1-predicted gene sequences was annotated as of Wolbachia or Wolbachia phage sourced from an arthropod. Clear evidence of exchange between sr1WOdamA1 and other Wolbachia

Larvas de simulídeos (Diptera, Simuliidae do centro oeste, sudeste e sul do Brasil, parasitadas por microsporídeos (Protozoa e mermitídeos (Nematoda Simulids larvae (Diptera, Simuliidae from middle western, southeastern and southern Brazil, with microsporids (Protozoa and mermithids (Nematoda parasites

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Carmen Ambrós Ginarte

2003-09-01

Full Text Available A survey of simulid larval parasites was carried out in different localities of the states of Mato Grosso, Minas Gerais, São Paulo, Paraná, Santa Catarina and Rio Grande do Sul, Brazil, from February 1996 to May 1998. Prevalences for the microsporidian Polydispyrenia simulii Lutz & Splendore, 1908 were found in Morungaba and Leme, São Paulo, ranging from around 0.7 to 66.7%, depending mainly on the host simulid species. Microsporidiosis was registered in localities of São Paulo, Paraná, Santa Catarina and Rio Grande do Sul. Parasitism by Isomermis sp. (Nematoda, Mermithidae was found in Simulium larvae from Serra do Japi, ranging from 0.8 to 45.8%, depending on the simulid species and the larval microhabitat in the stream, whether a cemented ramp in a lake outlet or the natural stream bed. Parasitism by mermithids was also found in ten localities. Mycoses caused by Coelomycidium sp. were for the first time recorded for larvae of Simulium (Chirostilbia pertinax Kollar, 1832.

Stability and change in the distribution of cytospecies of the Simulium damnosum complex (Diptera: Simuliidae) in southern Ghana from 1971 to 2011.

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Post, Rory J; Cheke, Robert A; Boakye, Daniel A; Wilson, Michael D; Osei-Atweneboana, Mike Y; Tetteh-Kumah, Anthony; Lamberton, Poppy Hl; Crainey, J Lee; Yaméogo, Laurent; Basáñez, María-Gloria

2013-07-13

Simulium damnosum s.l., the most important vector of onchocerciasis in Africa, is a complex of sibling species that have been described on the basis of differences in their larval polytene chromosomes. These (cyto) species differ in their geographical distributions, ecologies and epidemiological roles. In Ghana, distributional changes have been recorded as a consequence of vector control and environmental change (e.g. deforestation), with potential disease consequences. We review the distribution of cytospecies in southern Ghana and report changes observed with reference to historical data collated from 1971 to 2005 and new identifications made between 2006 and 2011. Larvae were collected from riverine breeding sites, fixed in Carnoy's solution and chromosome preparations made. Cytotaxonomic identifications from 1,232 samples (including 49 new samples) were analysed. We report long-term stability in cytospecies distribution in the rivers Afram, Akrum, Pawnpawn and Pru. For the rivers Oda, Ofin and Tano we describe (for the first time) patterns of distribution. We could not detect cytospecies composition changes in the upper Pra, and the lower Pra seems to have been stable. The elimination of the Djodji form of S. sanctipauli in the Volta Region seems to have had no long-term effects on the distribution of the other cytospecies, despite an initial surge by S. yahense. There has been a recent increase in the occurrence of savannah cytospecies in the river Asukawkaw, and this might be related to continuing deforestation. Cytospecies' distributions have not been stable from 1971 to 2011. Although there are no obvious causes for the temporary appearance and subsequent disappearance of cytospecies in a particular location, a major influence has been vector control and migration patterns, probably explaining observed changes on the Black Volta and lower Volta rivers. Deforestation was previously implicated in an increase of savannah cytospecies in southern Ghana (1975

Evaluation of the impact of Bacillus thuringiensis serovar israelensis and Temephos, used for the control of Simulium (Chirostilbia pertinax Kollar, 1832 (Diptera, Simuliidae on the associated entomofauna, Paraty, state of Rio de Janeiro, Brazil

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Araújo-Coutinho Carlos José Pereira da Cunha de

2003-01-01

Full Text Available The study was set up to evaluate the impact of two commercial larvicide formulations, Bacillus thuringiensis serovar israelensis base (Bti at 15 ppm/1 min and temephos at 0.03 ppm of active ingredient, used to control Simulium pertinax populations, on associated non-target entomofauna occupying the same breeding sites. The experiments were carried out on the Pedra Branca and Muricana rivers, on the slopes of Serra do Mar massif, municipality of Paraty, state of Rio de Janeiro, Brazil. Bti was applied to the river Pedra Branca and temephosto theriver Muricana. On both rivers, treatment and control sections were labeled as such, each one with two observation posts: slow moving water and fast water regions respectively. Artificial substrata was used to evaluate the abundance of associated entomofauna. Attached immature stages of arthropods were removed from both of its surfaces fortnightly. Were collected, from the two rivers, 28 477 specimens of the entomofauna associated with S. pertinax. The families Hydropsychidae, Chironomidae, Bactidae, Simuliidae, Blephariceridae and Megapodagrionidae were represented. These was an impact of temephos on the entomofauna associated with S. pertinax only in Simuliidae and Chironomidae, and to Bti only in Simuliidae. However, the reduction in their numbers was not statistically significant.

Evaluation of the impact of Bacillus thuringiensis serovar israelensis and Temephos, used for the control of Simulium (Chirostilbia) pertinax Kollar, 1832 (Diptera, Simuliidae) on the associated entomofauna, Paraty, state of Rio de Janeiro, Brazil.

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de Araújo-Coutinho, Carlos José Pereira da Cunha; Cunha, Andrea de Barros Pinto Viviani; Serra-Freire, Nicolau Maués; de Mello, Rubens Pinto

2003-07-01

The study was set up to evaluate the impact of two commercial larvicide formulations, Bacillus thuringiensis serovar israelensis base (Bti) at 15 ppm/1 min and temephos at 0.03 ppm of active ingredient, used to control Simulium pertinax populations, on associated non-target entomofauna occupying the same breeding sites. The experiments were carried out on the Pedra Branca and Muricana rivers, on the slopes of Serra do Mar massif, municipality of Paraty, state of Rio de Janeiro, Brazil. Bti was applied to the river Pedra Branca and temephosto theriver Muricana. On both rivers, treatment and control sections were labeled as such, each one with two observation posts: slow moving water and fast water regions respectively. Artificial substrata was used to evaluate the abundance of associated entomofauna. Attached immature stages of arthropods were removed from both of its surfaces fortnightly. Were collected, from the two rivers, 28 477 specimens of the entomofauna associated with S. pertinax. The families Hydropsychidae, Chironomidae, Bactidae, Simuliidae, Blephariceridae and Megapodagrionidae were represented. These was an impact of temephos on the entomofauna associated with S. pertinax only in Simuliidae and Chironomidae, and to Bti only in Simuliidae. However, the reduction in their numbers was not statistically significant.

Caractéristiques du développement larvaire de Simulium buissoni Roubaud, 1906 et de S. sechani Craig et Fossati, 1995 (Diptera : Simuliidae dans l'archipel des Marquises (Polynésie Française

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Séchan Y.

2001-03-01

Full Text Available Deux espèces de Simulies anthropophiles sévissent dans l'archipel des Marquises en Polynésie Française : Simulium buissoni Roubaud, 1906 et S . sechani Craig & Fossati, 1995. la nécessité de leur contrôle implique une meilleure connaissance de leur développement larvaire, les larves constituent en effet actuellement la seule phase du cycle susceptible d'être détruite. Une étude biométrique réalisée à partir de mesures des capsules céphaliques des larves des deux espèces montre qu'elles présentent toutes deux sept stades de développement. Les variations de taille suivant les espèces et les lieux de récoltes sont examinées, ainsi que les variations suivant le sexe pour les larves les plus âgées. Une expérience de recolonisation après traitement d'une section de rivière permet de déterminer que la durée de développement larvaire de S . buissoni est d'environ 12 jours. Ces données permettent de déterminer la fréquence optimale de traitement.

Chromosomal Translocations in Black Flies (Diptera: Simuliidae-Facilitators of Adaptive Radiation?

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Peter H Adler

Full Text Available A macrogenomic investigation of a Holarctic clade of black flies-the Simulium cholodkovskii lineage-provided a platform to explore the implications of a unique, synapomorphic whole-arm interchange in the evolution of black flies. Nearly 60 structural rearrangements were discovered in the polytene complement of the lineage, including 15 common to all 138 analyzed individuals, relative to the central sequence for the entire subgenus Simulium. Three species were represented, of which two Palearctic entities (Simulium cholodkovskii and S. decimatum were sympatric; an absence of hybrids confirmed their reproductive isolation. A third (Nearctic entity had nonhomologous sex chromosomes, relative to the other species, and is considered a separate species, for which the name Simulium nigricoxum is revalidated. A cytophylogeny is inferred and indicates that the two Palearctic taxa are sister species and these, in turn, are the sister group of the Nearctic species. The rise of the S. cholodkovskii lineage encompassed complex chromosomal and genomic restructuring phenomena associated with speciation in black flies, viz. expression of one and the same rearrangement as polymorphic, fixed, or sex linked in different species; taxon-specific differentiation of sex chromosomes; and reciprocal translocation of chromosome arms. The translocation is hypothesized to have occurred early in male spermatogonia, with the translocated chromosomal complement being transmitted to the X- and Y-bearing sperm during spermatogenesis, resulting in alternate disjunction of viable F1 translocation heterozygotes and the eventual formation of more viable and selectable F2 translocation homozygous progeny. Of 11 or 12 independently derived whole-arm interchanges known in the family Simuliidae, at least six are associated with subsequent speciation events, suggesting a facilitating role of translocations in adaptive radiations. The findings are discussed in the context of potential

Historia natural del virus de la estomatitis vesicular en zonas enzoóticas de Antioquia

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John Arboleda

2003-01-01

Full Text Available

La Estomatitis Vesicular (EV es una enfermedad producida
por el virus de la Estomatitis Vesicular, serotipos New Jersey (VSV-NJ e Indiana (VSV-IN, afecta bovinos y equinos, porcinos y causa infección natural en humanos, principalmente granjeros, ordeñadores y personal de laboratorio.
Se caracteriza por producir vesículas en las membranas mucosas
de la boca (epitelio de la lengua y el paladar, bandas coronarias,
pezones y tejidos blandos de los cascos; hay pérdida de peso y decrecimiento en la producción de leche. Está clasificada en la Lista A de la Organización Internacional de Epizootias, debido a su gran poder de difusión, a las graves consecuencias socioeconómicas y a las restricciones comerciales. Además, clínicamente la EV es indistinguible de la Fiebre Aftosa (FA (1.
La enfermedad se presenta por ciclos estacionales; la mayoría
de ellos ocurre en las épocas de transición de los períodos de lluvias a los de verano y viceversa (2. Estudios serológicos realizados en áreas endémicas han demostrado que VSV-NJ y VSV-IN infectan en forma natural una amplia variedad de animales silvestres, los cuales están posiblemente implicados en la ecozootiología de la EV, bien como hospederos portadores, amplificadores o reservorios. Igualmente, dos especies de artrópodos, Lutzomyia shannoni y Simulium vittatum son infectados naturalmente, replican y transmiten experimentalmente
el VSV, convirtiéndolos en posibles vectores y/o reservorios.
Sin embargo, en ningún animal se produce la viremia necesaria para infectar los artrópodos hematófagos. El reservorio natural nunca ha sido encontrado entre los animales domésticos y silvestres investigados (3.

El objetivo es identificar los factores ecológicos (cobertura
vegetal, temperatura promedio, pluviosidad y humedad relativa, los vectores artrópodos y los mamíferos reservorios asociados con el antenimiento y transmisión de la VSV en

Windows 7 is supported at CERN

CERN Multimedia

IT Department

2010-01-01

The new version of the Windows operating system - Windows 7 - is now officially supported at CERN. Windows 7 32-bit is now the default operating system for the new computers at CERN. What’s new in Windows 7 Users of Windows XP will find many new features and options. Users of Windows Vista will feel very familiar with one major difference: higher performance and better responsiveness of the operating system. Other enhancements include: refined Aero desktop that makes it easier to navigate between your different application windows; new snapping windows that allows user to resize a window simply by dragging it to the edge of the screen and “pin” that allows grouping and arranging often accessed applications on the taskbar. Windows 7 introduces the new concept of libraries – containers for user files that have links to different local or network folders. By default, users can see four libraries: Documents, Music, Pictures and Videos. These libraries point to the cor...

Onchocerciasis (River Blindness) FAQs

Science.gov (United States)

... an infection caused by the parasitic worm Onchocerca volvulus , spread by the bite of an infected Simulium ... indicate that you are still infected with O. volvulus . What is the treatment for onchocerciasis? There are ...

African Journal of Science and Technology (AJST ...

African Journals Online (AJOL)

Administrator

the disease bring about the need to control onchocerciasis by understanding the mechanism of the host's ... The insect vector of Onchocerca is the black fly, Simulium. The larvae ...... D. immitis infection in dogs (WHO, 1987). Introduction of.

Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci.

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Isam M A Zarroug

Full Text Available The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs.A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010. Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests.Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies than Galabat (8,202 flies. In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month, and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month while none of flies were collected in August-October (MBR = 0 bites/person/month. In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month and September 2010 (N = 1,163, MBR = 6,978 bites/person/month, whereas, none appeared in collection from April to

Parasites of larval black flies (Diptera: Simuliidae in Thailand

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Sanae Jitklang

2012-12-01

Full Text Available Parasites of larval black flies are reported for the first time from Thailand, including mermithid nematodes(Mermithidae, microsporidian fungi (Zygomycota, and the fungus Coelomycidium simulii Debaisieux (Blastocladiomycetes.The following nine species of black flies were infected with one or more parasites: Simulium asakoae, S. chamlongi,S. chiangmaiense, S. fenestratum, S. feuerborni, S. nakhonense, S. nodosum, S. quinquestriatum, and S. tani. The prevalenceof patent infections per host species per season was 0.1–7.1% for mermithids, 0.1–6.0% for microsporidia, and 0.1–3.0% forC. simulii.

ONCHOCERCIASIS – A PUBLIC HEALTH PERSPECTIVE ...

African Journals Online (AJOL)

Onchocerciasis is a chronic parasitic disease with a wide range of cutaneous and ocular manifestations. It is caused by the tissue nematode, Onchocerca volvulus, and it is transmitted by the bite of a female black fly, Simulium damnosum. Onchocerciasis is a serious public health and socio-economic problem with 95% of all ...

Stability Analysis of a Mathematical Model for Onchocerciaisis ...

African Journals Online (AJOL)

ADOWIE PERE

ABSTRACT: In this work, we propose a Deterministic Mathematical Model that ... blackflies Center for Disease Control and World ... villages located along fast flowing rivers where the ..... distribution of Blackflies (Simulium Species) in.

The vectoral role of several blackfly species (Diptera: Simuliidae) in relation to human onchocerciasis in the Sierra Parima and Upper Orinoco regions of Venezuela.

Science.gov (United States)

Basáñez, M G; Yarzábal, L; Takaoka, H; Suzuki, H; Noda, S; Tada, I

1988-12-01

Experimental and natural infections with Onchocerca volvulus were studied in several anthropophilic blackfly species present in the endemic area of the Upper Orinoco region of Venezuela. When fed on four different Yanomami volunteers in the Sierra Parima, the total infection rate was 31.4% for Simulium guianense in comparison with 7.5% for S. limbatum. The proportion of ingested microfilariae that entered the thorax during the first 24 hours and completed development to the infective stage was also much lower in the latter than in the former species. There was no larval development of O. volvulus in S. antillarum, but one female harboured in its head six infective larvae of a zoonotic filaria. When S. oyapokense s.l. was fed on an infected volunteer in the Upper Orinoco most flies ingested few microfilariae, and further development reached only the L1 stage. Natural infection and infectivity rates for S. guianense in two localities of the Sierra Parima were 0.2-4.0% and 1.3-10.2%, respectively, more than 50% of the L3 larvae being in the head. The corresponding data for S. oyapockense s.l. in the Upper Orinoco were 0.1-0.5%, although the only L3 larva found did not correspond to O. volvulus. It is suggested that S. guianense is the main vector of onchocerciasis in the Sierra Parima and that S. limbatum could play a secondary role. Simulium oyapockense s.l. replaces them in the Upper Orinoco and may maintain a degree of transmission, but its epidemiological importance remains to be assessed.

Prevalence of Concomitant Onchocerciasis-Malaria Infection in ...

African Journals Online (AJOL)

2012 to April 2014 to ascertain the prevalence of onchocerciasis-malaria co-infec on. Four hundred and ... features with ophthalmic signs often presen ng several years .... breeding of both Simulium damnosum and Anopheles mosquitoes ...

"Jejenes" (Diptera: Simuliidae of Nahuel Huapi National Park, Patagonia, Argentina: Preliminary results "Jejenes" (Diptera: Simuliidae del Parque Nacional Nahuel Huapi, Patagonia, Argentina: Resultados preliminares

Directory of Open Access Journals (Sweden)

Luis M. Hernández

2009-06-01

Full Text Available The Simuliidae is a family of Diptera with approximately 2072 described species worldwide. The females of the majority of the species feed from vertebrates' blood, which makes them a significant plague that affects both men as well as cattle, birds, and other vertebrates. The objective of this paper is to create an inventory of Simuliidae and to reveal certain aspects of the biology and distribution of this family of aquatic insects in the Nahuel Huapi National Park. Moreover, information on the zoogeography of Simuliidae in Patagonia is provided. Five genera, 3 subgenera and 32 species Simuliidae are recorded from Patagonia: Cnesia (three spp., Cnesiamima (one sp., Gigantodax (14 spp., Paraustrosimulium (one sp., Simulium (Ectemnaspis (one sp., S. (Psaroniocompsa (one sp. and S. ( Pternaspatha (11 spp., At present, we have collected all five genera, one subgenus of Simulium (Pternaspatha, and 19 species of Simuliidae in the park, which amounts to 57% of the Simuliidae fauna in this area. Puerto Blest, a characteristic area of the High-Andean phytogeographical province (humid forest, showed the highest diversity of Simuliidae.Los simúlidos pertenecen a una familia de Diptera (Simuliidae con alrededor de 2.072 especies descritas a nivel mundial. Las hembras de la mayoría de las especies se alimentan con sangre de vertebrados, lo cual las convierte en importantes plagas que afectan tanto al hombre como al ganado, aves y otros vertebrados. Los objetivos de este trabajo son llevar a cabo un inventario de Simuliidae y dar a conocer algunos aspectos de la biología y la distribución de esta familia de insectos acuáticos en el Parque Nacional Nahuel Huapi, Argentina. Además, se proporciona información sobre la biogeografía de Simuliidae en la Patagonia. Cinco géneros, un subgénero y 32 especies de simúlidos han sido registrados para Patagonia: Cnesia (3 spp., Cnesiamima (1 sp., Gigantodax (14 spp., Paraustrosimulium (1 sp., Simulium

African Journal of Aquatic Science - Vol 31, No 2 (2006)

African Journals Online (AJOL)

Estimation of preferred water flow parameters for four species of Simulium ... The distribution and abundance of the endangered Knysna seahorse ... The food and feeding habits of five freshwater and brackish-water fish species in Nigeria ...

Vietnam, a Hotspot for Chromosomal Diversity and Cryptic Species in Black Flies (Diptera: Simuliidae)

Science.gov (United States)

Takaoka, Hiroyuki; Sofian-Azirun, Mohd; Low, Van Lun; Ya’cob, Zubaidah; Chen, Chee Dhang; Lau, Koon Weng; Pham, Xuan Da

2016-01-01

The increasing attention on Vietnam as a biodiversity hotspot prompted an investigation of the potential for cryptic diversity in black flies, a group well known elsewhere for its high frequency of isomorphic species. We analyzed the banding structure of the larval polytene chromosomes in the Simulium tuberosum species group to probe for diversity beyond the morphological level. Among 272 larvae, 88 different chromosomal rearrangements, primarily paracentric inversions, were discovered in addition to 25 already known in the basic sequences of the group in Asia. Chromosomal diversity in Vietnam far exceeds that known for the group in Thailand, with only about 5% of the rearrangements shared between the two countries. Fifteen cytoforms and nine morphoforms were revealed among six nominal species in Vietnam. Chromosomal evidence, combined with available molecular and morphological evidence, conservatively suggests that at least five of the cytoforms are valid species, two of which require formal names. The total chromosomal rearrangements and species (15) now known from the group in Vietnam far exceed those of any other area of comparable size in the world, supporting the country’s status as a biodiversity hotspot. Phylogenetic inference based on uniquely shared, derived chromosomal rearrangements supports the clustering of cytoforms into two primary lineages, the Simulium tani complex and the Southeast Asian Simulium tuberosum subgroup. Some of these taxa could be threatened by habitat destruction, given their restricted geographical distributions and the expanding human population of Vietnam. PMID:27695048

USP7 is a SUMO deubiquitinase essential for DNA replication

Science.gov (United States)

Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia; Lopez-Contreras, Andres J; Ruppen, Isabel; Murga, Matilde; Muñoz, Javier; Mendez, Juan; Fernandez-Capetillo, Oscar

2016-01-01

Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates various aspects of DNA replication. We previously showed that the chromatin around replisomes is rich in SUMO and depleted in Ub, whereas an opposite pattern is observed in mature chromatin. How this SUMO-rich/Ub-low environment is maintained at sites of DNA replication is not known. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Chemical inhibition or genetic deletion of USP7 leads to the accumulation of Ub on SUMOylated proteins, which are displaced to chromatin away from replisomes. Our findings provide a model to explain the differential accumulation of SUMO and Ub at replication forks, and identify an essential role of USP7 in DNA replication that should be taken into account for the use of USP7 inhibitors as anticancer agents. PMID:26950370

USP7 is a SUMO deubiquitinase essential for DNA replication

DEFF Research Database (Denmark)

Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia

2016-01-01

Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment...... is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads...... to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7...

Human disc degeneration is associated with increased MMP 7 expression.

Science.gov (United States)

Le Maitre, C L; Freemont, A J; Hoyland, J A

2006-01-01

During intervertebral disc (IVD) degeneration, normal matrix synthesis decreases and degradation of disc matrix increases. A number of proteases that are increased during disc degeneration are thought to be involved in its pathogenesis. Matrix metalloproteinase 7 (MMP 7) (Matrilysin, PUMP-1) is known to cleave the major matrix molecules found within the IVD, i.e., the proteoglycan aggrecan and collagen type II. To date, however, it is not known how its expression changes with degeneration or its exact location. We investigated the localization of MMP 7 in human, histologically graded, nondegenerate, degenerated and prolapsed discs to ascertain whether MMP 7 is up-regulated during disc degeneration. Samples of human IVD tissue were fixed in neutral buffered formalin, embedded in paraffin, and sections stained with hematoxylin and eosin to score the degree of morphological degeneration. Immunohistochemistry was performed to localize MMP 7 in 41 human IVDs with varying degrees of degeneration. We found that the chondrocyte-like cells of the nucleus pulposus and inner annulus fibrosus were MMP 7 immunopositive; little immunopositivity was observed in the outer annulus. Nondegenerate discs showed few immunopositive cells. A significant increase in the proportion of MMP 7 immunopositive cells was seen in the nucleus pulposus of discs classified as showing intermediate levels of degeneration and a further increase was seen in discs with severe degeneration. Prolapsed discs showed more MMP 7 immunopositive cells compared to nondegenerated discs, but fewer than those seen in cases of severe degeneration.

Galectin-7 is important for normal uterine repair following menstruation.

Science.gov (United States)

Evans, Jemma; Yap, Joanne; Gamage, Thillini; Salamonsen, Lois; Dimitriadis, Evdokia; Menkhorst, Ellen

2014-08-01

Menstruation involves the shedding of the functional layer of the endometrium in the absence of pregnancy. At sites where tissue shedding is complete, re-epithelialization of the tissue is essential for repair and termination of bleeding. The complement of growth factors that mediate post-menstrual endometrial repair are yet to be completely elucidated. Galectins regulate many cell functions important for post-menstrual repair, such as cell adhesion and migration. Galectin-7 has a well characterized role in re-epithelialization and wound healing. We hypothesized that galectin-7 would be important in re-epithelialization during post-menstrual repair. We aimed to identify endometrial expression of galectin-7 in women undergoing normal endometrial repair and in women with amenorrhoea who do not experience endometrial breakdown and repair, and to determine whether galectin-7 enhances endometrial re-epithelialization in vitro. Galectin-7 immunolocalized to the endometrial luminal and glandular epithelium during the late secretory and menstrual phases, and to decidualized stroma in regions exhibiting tissue breakdown. Immunostaining intensity was significantly reduced in the endometrium of women with amenorrhoea compared with normally cycling woman. ELISA identified galectin-7 in menstrual fluid at significantly elevated levels compared with matched peripheral plasma. Exogenous galectin-7 (2.5 µg/ml) significantly enhanced endometrial epithelial wound repair in vitro; this was abrogated by inhibition of integrin binding. Galectin-7 elevated epithelial expression of extracellular matrix-related molecules likely involved in repair including β-catenin, contactin and TGF-β1. In conclusion, galectin-7 is produced by the premenstrual and menstrual endometrium, where it accumulates in menstrual fluid and likely acts as a paracrine factor to facilitate post-menstrual endometrial re-epithelialization. © The Author 2014. Published by Oxford University Press on behalf of the

7 CFR 1783.7 - What is the grant application process?

Science.gov (United States)

2010-01-01

... 1783.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE...: Standard Form 424A; (3) Assurances—Non-Construction Programs: Standard Form 424B; (4) Evidence of applicant... (6) Most recent annual audit conducted by an independent auditor. (b) The applicant must submit a...

7 CFR 29.57 - Where inspection is offered.

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2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Where inspection is offered. 29.57 Section 29.57... REGULATIONS TOBACCO INSPECTION Regulations Permissive Inspection § 29.57 Where inspection is offered. Tobacco..., samplers, or weighers are available and the tobacco is offered under conditions that permit of its proper...

7 CFR 58.5 - Where service is offered.

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2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Where service is offered. 58.5 Section 58.5 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Grading Service § 58.5 Where service is offered. Subject to the provisions of this part, inspection or...

Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo

Energy Technology Data Exchange (ETDEWEB)

Cheong, Chee Man [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Chow, Annie W.S. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); Fitter, Stephen [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Hewett, Duncan R. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); School of Medicine, University of Adelaide, Adelaide 5005, SA (Australia); Martin, Sally K. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); School of Medicine, University of Adelaide, Adelaide 5005, SA (Australia); Williams, Sharon A. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); To, L. Bik [Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); and others

2015-03-01

Background: Increased expression of the tetraspanin TSPAN7 has been observed in a number of cancers; however, it is unclear how TSPAN7 plays a role in cancer progression. Methods: We investigated the expression of TSPAN7 in the haematological malignancy multiple myleoma (MM) and assessed the consequences of TSPAN7 expression in the adhesion, migration and growth of MM plasma cells (PC) in vitro and in bone marrow (BM) homing and tumour growth in vivo. Finally, we characterised the association of TSPAN7 with cell surface partner molecules in vitro. Results: TSPAN7 was found to be highly expressed at the RNA and protein level in CD138{sup +} MM PC from approximately 50% of MM patients. TSPAN7 overexpression in the murine myeloma cell line 5TGM1 significantly reduced tumour burden in 5TGM1/KaLwRij mice 4 weeks after intravenous adminstration of 5TGM1 cells. While TSPAN7 overexpression did not affect cell proliferation in vitro, TSPAN7 increased 5TGM1 cell adhesion to BM stromal cells and transendothelial migration. In addition, TSPAN7 was found to associate with the molecular chaperone calnexin on the cell surface. Conclusion: These results suggest that elevated TSPAN7 may be associated with better outcomes for up to 50% of MM patients. - Highlights: • TSPAN7 expression is upregulated in newly-diagnosed patients with active multiple myeloma. • Overexpression of TSPAN7 inhibits myeloma tumour development in vivo. • TSPAN7 interacts with calnexin at the plasma membrane in a myeloma cell line.

Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer

International Nuclear Information System (INIS)

Ramani, Vishnu C; Hennings, Leah; Haun, Randy S

2008-01-01

In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (KLK7/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells. The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using in vitro degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2. The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells. A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using in vitro degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion

Author Details

African Journals Online (AJOL)

Factors affecting the transmission of human onchocerciasis by Simulium damnosum s l. in a fringe savanna village in Cross River State, Nigeria Abstract · Vol 9, No 1 (2009) - Articles Histochemical Characterization of Rain-Forest Strain of Onchocerca Volvulus Microfilariae Isolated in Akamkpa, Cross River State, Nigeria.

41 CFR 301-74.7 - What is the conference lodging allowance?

Science.gov (United States)

2010-07-01

... lodging allowance? 301-74.7 Section 301-74.7 Public Contracts and Property Management Federal Travel Regulation System TEMPORARY DUTY (TDY) TRAVEL ALLOWANCES AGENCY RESPONSIBILITIES 74-CONFERENCE PLANNING Agency Responsibilities § 301-74.7 What is the conference lodging allowance? The conference lodging...

Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

Directory of Open Access Journals (Sweden)

Lemtiri-Chlieh Fouad

2011-12-01

Full Text Available Abstract Background Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP, widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7, a Rho GDP/GTP exchange factor (Rho-GEF localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7KO have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments. Results We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7. Conclusions These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus.

Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

KAUST Repository

Lemtiri-Chlieh, Fouad

2011-12-19

Background: Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7 KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments.Results: We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7.Conclusions: These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus. 2011 Lemtiri-Chlieh et al; licensee BioMed Central Ltd.

Biallelic inactivation of REV7 is associated with Fanconi anemia.

Science.gov (United States)

Bluteau, Dominique; Masliah-Planchon, Julien; Clairmont, Connor; Rousseau, Alix; Ceccaldi, Raphael; Dubois d'Enghien, Catherine; Bluteau, Olivier; Cuccuini, Wendy; Gachet, Stéphanie; Peffault de Latour, Régis; Leblanc, Thierry; Socié, Gérard; Baruchel, André; Stoppa-Lyonnet, Dominique; D'Andrea, Alan D; Soulier, Jean

2016-09-01

Fanconi anemia (FA) is a recessive genetic disease characterized by congenital abnormalities, chromosome instability, progressive bone marrow failure (BMF), and a strong predisposition to cancer. Twenty FA genes have been identified, and the FANC proteins they encode cooperate in a common pathway that regulates DNA crosslink repair and replication fork stability. We identified a child with severe BMF who harbored biallelic inactivating mutations of the translesion DNA synthesis (TLS) gene REV7 (also known as MAD2L2), which encodes the mutant REV7 protein REV7-V85E. Patient-derived cells demonstrated an extended FA phenotype, which included increased chromosome breaks and G2/M accumulation upon exposure to DNA crosslinking agents, γH2AX and 53BP1 foci accumulation, and enhanced p53/p21 activation relative to cells derived from healthy patients. Expression of WT REV7 restored normal cellular and functional phenotypes in the patient's cells, and CRISPR/Cas9 inactivation of REV7 in a non-FA human cell line produced an FA phenotype. Finally, silencing Rev7 in primary hematopoietic cells impaired progenitor function, suggesting that the DNA repair defect underlies the development of BMF in FA. Taken together, our genetic and functional analyses identified REV7 as a previously undescribed FA gene, which we term FANCV.

Author Details

African Journals Online (AJOL)

Ejezie, GC. Vol 5, No 2 (2005) - Articles Factors affecting the transmission of human onchocerciasis by Simulium damnosum s l. in a fringe savanna village in Cross River State, Nigeria Abstract · Vol 1 (2000) - Articles Nutritional Status of Pre-School Children in Rural Nigeria: Relationships with Intestinal Helminthiasis

Kv7.1 surface expression is regulated by epithelial cell polarization

DEFF Research Database (Denmark)

Andersen, Martin N; Olesen, Søren-Peter; Rasmussen, Hanne Borger

2011-01-01

The potassium channel K(V)7.1 is expressed in the heart where it contributes to the repolarization of the cardiac action potential. In addition, K(V)7.1 is expressed in epithelial tissues where it plays a role in salt and water transport. Mutations in the kcnq1 gene can lead to long QT syndrome...... and deafness, and several mutations have been described as trafficking mutations. To learn more about the basic mechanisms that regulate K(V)7.1 surface expression, we have investigated the trafficking of K(V)7.1 during the polarization process of the epithelial cell line Madin-Darby Canine Kidney (MDCK) using...... is regulated by signaling mechanisms involved in epithelial cell polarization in particular signaling cascades involving protein kinase C and PI3K....

Expression of kallikrein-related peptidase 7 is decreased in prostate cancer

Directory of Open Access Journals (Sweden)

Chong-Yu Zhang

2015-02-01

Full Text Available Recent evidence suggests that the human kallikrein 7 (KLK7 is differentially regulated in a variety of tumors. The aim of this study was to determine the expression of kallikrein-related peptidase 7 and KLK7 in our large collection of prostate samples. Between August 2000 and December 2012, 116 patients with histologically confirmed prostate cancer (PCa and 92 with benign prostate hyperplasia (BPH were recruited into the study. Using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-PCR and western blot, kallikrein-related peptidase 7 expression in BPH and PCa tissues was determined at the mRNA and protein levels. The relationships between kallikrein-related peptidase 7 mRNA expression and clinicopathological features were analyzed. A total of 64 of 92 (69.57% benign cases showed positive staining for KLK7 and 23 of 116 (19.83% malignant cases showed positive, the difference of KLK7 expression between PCa and BPH was statistically significant (P < 0.001. The expression level of kallikrein-related peptidase 7 mRNA was significantly decreased in PCa tissues compared with that in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 mRNA exhibited different expression patterns in terms of localization depending on pathological category of PCa. Similarly, our western immunoblot analyses demonstrated that the protein expression levels of KLK7 was lower in PCa than in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 and KLK7 expression are down-regulated in PCa and lower expression of kallikrein-related peptidase 7 closely correlates with higher Gleason score and higher prostate-specific antigen level.

The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function.

Science.gov (United States)

Araud, Tanguy; Graw, Sharon; Berger, Ralph; Lee, Michael; Neveu, Estele; Bertrand, Daniel; Leonard, Sherry

2011-10-15

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [(125)I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of α7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with α7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of winter flow regulation on pest-level populations of blackfly ...

African Journals Online (AJOL)

The mid-reaches of the Great Fish River in the Eastern Cape Province of South Africa experience regular outbreaks of the pest blackfly Simulium chutteri as a direct consequence of increased flows caused by an inter-basin transfer scheme. There are opportunities to control these outbreaks through flow manipulation by ...

TRPM7 is required for ovarian cancer cell growth, migration and invasion

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Wang, Jing; Liao, Qian-jin [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Yi [Department of Obstetrics and Gynaecology, Xiangya Hospital, Central South University, Changsha 410078 (China); Zhou, Hui; Luo, Chen-hui; Tang, Jie; Wang, Ying; Tang, Yan; Zhao, Min; Zhao, Xue-heng [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Qiong-yu [Department of Basic Medical Science, Yongzhou Vocational Technical College, Yong Zhou 425100 (China); Xiao, Ling, E-mail: lingxiaocsu@126.com [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013 (China); Institute of Clinical Pharmacology, Central South University, Changsha 410018 (China)

2014-11-28

Highlights: • Silence of TRPM7 in ovarian cancer cells inhibits cell proliferation, migration and invasion. • Silence of TRPM7 decreases phosphorylation levels of Akt, Src and p38 in ovarian cancer cells. • Silence of TRPM7 increases expression of filamentous actin and number of focal adhesions in ovarian cancer cells. - Abstract: Our previous study demonstrated that the melastatin-related transient receptor potential channel 7 (TRPM7) was highly expressed in ovarian carcinomas and its overexpression was significantly associated with poor prognosis in ovarian cancer patients. However, the function of TRPM7 in ovarian cancer is mostly unknown. In this study, we examined the roles of TRPM7 in ovarian cancer cell proliferation, migration and invasion. We found that short hairpin RNA interference-mediated silence of TRPM7 significantly inhibited cell proliferation, colony formation, migration and invasion in multiple ovarian cancer cell lines. Mechanistic investigation revealed that silence of TRPM7 decreased phosphorylation levels of Akt, Src and p38 and increased filamentous actin and focal adhesion number in ovarian cancer cells. Thus, our results suggest that TRPM7 is required for proliferation, migration and invasion of ovarian cancer cells through regulating multiple signaling transduction pathways and the formation of focal adhesions.

Leucocytozoonosis in Canada Geese at the Seney National Wildlife Refuge

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Herman, C.M.; Barrow, J.H.; Tarshis, I.B.

1975-01-01

A history is given of the Seney National Wildlife Refuge and the losses of goslings of Canada geese (Branta canadensis) recorded since inception of the refuge in 1935. Since 1960, when more reliable data became available, losses have been extensive every 4 years. Gosling deaths are attributed to the infection with Leucocytozoon simondi. The blackfly (Simulium innocens) is considered to be the prime vector in the transmission of this blood parasite to goslings.

Author Details

African Journals Online (AJOL)

Opoku, AA. Vol 13, No 1 (2008) - Articles The Effect of C02, Sweat, Chemical Vapours and Air on Simulium ornatum: Implications for Control Abstract PDF · Vol 9, No 1 (2006) - Articles The ecology and biting activity of blackflies (Simuliidae) and the prevalence of onchocerciasis in an agricultural community in Ghana

SmATG7 is required for viability in the homothallic ascomycete Sordaria macrospora.

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Nolting, Nicole; Bernhards, Yasmine; Pöggeler, Stefanie

2009-08-01

In filamentous ascomycetes, autophagy is involved in several developmental processes. Nevertheless, until now little is known about its role in fruiting-body development. We therefore isolated a gene of the homothallic ascomycete Sordaria macrospora with high sequence similarity to the Saccharomyces cerevisiae autophagy-related gene ATG7, encoding a core autophagy regulator. This is the first characterization of an ATG7 homolog in filamentous ascomycetes. A S. cerevisiae complementation assay demonstrated that the S. macrospora Smatg7 gene functionally replaces the yeast homolog. We were not able to generate a homokaryotic knock-out mutant in S. macrospora, suggesting that Smatg7 is required for viability. However, a heterokaryotic DeltaSmatg7/Smatg7 strain and transformants generated by RNA interference showed considerable morphological phenotypes during fruiting-body development. Using real-time PCR, we demonstrated that in the wild type, the transcriptional expression of Smatg7 is markedly up-regulated under amino acid starvation conditions and at late stages during sexual development. Moreover, we showed that transcriptionally down-regulation of Smatg7 disturbs autophagy in S. macrospora.

Fear and loathing in the benthos: Responses of aquatic insect larvae to the pesticide imidacloprid in the presence of chemical signals of predation risk.

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Pestana, João L T; Loureiro, Susana; Baird, Donald J; Soares, Amadeu M V M

2009-06-28

The influence of interactions between pesticide exposure and perceived predation risk on the lethal and sub-lethal responses of two aquatic insects was investigated using the pesticide imidacloprid, and a combination of predator-release kairomones from trout and alarm substances from conspecifics. Laboratory experiments examined feeding and respiration rates of the caddisfly Sericostoma vittatum as well as the growth, emergence and respiration rates of the midge Chironomus riparius, exposed to sub-lethal concentrations of imidacloprid. The effects of the two stressors on burrowing behaviour of both species were also assessed. The results show significant effects of environmentally relevant concentrations of imidacloprid on all endpoints studied. Perceived predation risk also elicited sub-lethal effects in C. riparius and S. vittatum, the latter species being less responsive to predation cues. The effects of simultaneous exposure to both types of stressors were assessed using two different approaches: analysis of variance and conceptual models [concentration addition (CA) and independent action (IA)] normally used for the evaluation of contaminant mixture exposure. Both statistical approaches showed no significant interactions on responses in simultaneous exposures in the majority of parameters assessed with only a signification deviation from the reference CA and IA models being found for C. riparius respiration data contrary to the ANOVA results. Exposure to imidacloprid also compromised antipredator behavioural responses of both insect species, with potential negative consequences in terms of mortality from predation in the field. The results obtained demonstrate that natural and anthropogenic stressors can be treated within the same framework providing compatible data for modelling. For an improved interpretation of ecological effects it will be important to expand the mechanistic study of effects of combined exposure to pesticides and perceived predation risk

Vesicle-associated membrane protein 7 (VAMP-7) is essential for target cell killing in a natural killer cell line

International Nuclear Information System (INIS)

Marcet-Palacios, Marcelo; Odemuyiwa, Solomon O.; Coughlin, Jason J.; Garofoli, Daniella; Ewen, Catherine; Davidson, Courtney E.; Ghaffari, Mazyar; Kane, Kevin P.; Lacy, Paige; Logan, Michael R.; Befus, A. Dean; Bleackley, R. Chris; Moqbel, Redwan

2008-01-01

Natural killer cells recognize and induce apoptosis in foreign, transformed or virus-infected cells through the release of perforin and granzymes from secretory lysosomes. Clinically, NK-cell mediated killing is a major limitation to successful allo- and xenotransplantation. The molecular mechanisms that regulate the fusion of granzyme B-containing secretory lysosomes to the plasma membrane in activated NK cells, prior to target cell killing, are not fully understood. Using the NK cell line YT-Indy as a model, we have investigated the expression of SNAP REceptors (SNAREs), both target (t-) and vesicular (v-) SNAREs, and their function in granzyme B-mediated target cell killing. Our data showed that YT-Indy cells express VAMP-7 and SNAP-23, but not VAMP-2. VAMP-7 was associated with granzyme B-containing lysosomal granules. Using VAMP-7 small interfering RNA (siRNA), we successfully knocked down the expression of VAMP-7 protein in YT-Indy to less than 10% of untreated cells in 24 h. VAMP7-deficient YT-Indy cells activated via co-culture with Jurkat cells released <1 ng/mL of granzyme B, compared to 1.5-2.5 μg/mL from controls. Using Jurkat cells as targets, we showed a 7-fold reduction in NK cell-mediated killing by VAMP-7 deficient YT-Indy cells. Our results show that VAMP-7 is a crucial component of granzyme B release and target cell killing in the NK cell line YT-Indy. Thus, targeting VAMP-7 expression specifically with siRNA, following transplantation, may be a viable strategy for preventing NK cell-mediated transplant rejection, in vivo

Onchocerca volvulus-neurotransmitter tyramine is a biomarker for river blindness.

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Globisch, Daniel; Moreno, Amira Y; Hixon, Mark S; Nunes, Ashlee A K; Denery, Judith R; Specht, Sabine; Hoerauf, Achim; Janda, Kim D

2013-03-12

Onchocerciasis, also known as "river blindness", is a neglected tropical disease infecting millions of people mainly in Africa and the Middle East but also in South America and Central America. Disease infectivity initiates from the filarial parasitic nematode Onchocerca volvulus, which is transmitted by the blackfly vector Simulium sp. carrying infectious third-stage larvae. Ivermectin has controlled transmission of microfilariae, with an African Program elimination target date of 2025. However, there is currently no point-of-care diagnostic that can distinguish the burden of infection--including active and/or past infection--and enable the elimination program to be effectively monitored. Here, we describe how liquid chromatography-MS-based urine metabolome analysis can be exploited for the identification of a unique biomarker, N-acetyltyramine-O,β-glucuronide (NATOG), a neurotransmitter-derived secretion metabolite from O. volvulus. The regulation of this tyramine neurotransmitter was found to be linked to patient disease infection, including the controversial antibiotic doxycycline treatment that has been shown to both sterilize and kill adult female worms. Further clues to its regulation have been elucidated through biosynthetic pathway determination within the nematode and its human host. Our results demonstrate that NATOG tracks O. volvulus metabolism in both worms and humans, and thus can be considered a host-specific biomarker for onchocerciasis progression. Liquid chromatography-MS-based urine metabolome analysis discovery of NATOG not only has broad implications for a noninvasive host-specific onchocerciasis diagnostic but provides a basis for the metabolome mining of other neglected tropical diseases for the discovery of distinct biomarkers and monitoring of disease progression.

Overexpression of Cullin7 is associated with hepatocellular carcinoma progression and pathogenesis.

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An, Jun; Zhang, Zhigang; Liu, Zhiyong; Wang, Ruizhi; Hui, Dayang; Jin, Yi

2017-12-06

Overexpression of Cullin7 is associated with some types of malignancies. However, the part of Cullin7 in hepatocellular carcinoma remains unclear. The aim of this study was to investigate the role of Cullin7 in pathogenesis and the progression of hepatocellular carcinoma. In the present study, the expression of Cullin7 in hepatocellular carcinoma cell lines and five surgical hepatocellular carcinoma specimens was detected with quantitative reverse transcription PCR and western blotting. In addition, the protein expression of Cullin7 was examined in 162 cases of archived hepatocellular carcinoma using immunohistochemistry. We found elevated expression of both mRNA and protein levels of Cullin7 in hepatocellular carcinoma cell lines, and Cullin7 protein was significantly upregulated in hepatocellular carcinoma compared with paired normal hepatic tissues. The immunohistochemistry analysis revealed that overexpression of Cullin7 occurred in 69.1% of hepatocellular carcinoma samples, which was a significantly higher rate than that in adjacent normal hepatic tissue (P hepatocellular carcinoma HepG2 cells, we revealed that Cullin7 could significantly enhance cell proliferation, growth, migration and invasion. Conversely, knocking down Cullin7 expression with short hairpin RNAi in hepatocellular carcinoma HepG2 cells inhibited cell proliferation, growth, migration and invasion. Our studies provide evidence that overexpression of Cullin7 plays an important role in the pathogenesis and progression of hepatocellular carcinoma and may be a valuable marker for hepatocellular carcinoma management.

Nav1.7 expression is increased in painful human dental pulp

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Levinson S Rock

2008-04-01

Full Text Available Abstract Background Animal studies and a few human studies have shown a change in sodium channel (NaCh expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth as a model system to study peripheral pain mechanisms and here examine the expression of the Nav1.7 NaCh isoform in normal and painful samples. Pulpal sections were labeled with antibodies against: 1 Nav1.7, N52 and PGP9.5, and 2 Nav1.7, caspr (a paranodal protein used to identify nodes of Ranvier, and myelin basic protein (MBP, and a z-series of optically-sectioned images were obtained with the confocal microscope. Nav1.7-immunofluorescence was quantified in N52/PGP9.5-identified nerve fibers with NIH ImageJ software, while Nav1.7 expression in myelinated fibers at caspr-identified nodal sites was evaluated and further characterized as either typical or atypical as based on caspr-relationships. Results Results show a significant increase in nerve area with Nav1.7 expression within coronal and radicular fiber bundles and increased expression at typical and atypical caspr-identified nodal sites in painful samples. Painful samples also showed an augmentation of Nav1.7 within localized areas that lacked MBP, including those associated with atypical caspr-identified sites, thus identifying NaCh remodeling within demyelinating axons as the basis for a possible pulpal pain mechanism. Conclusion This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to constant, increased evoked and spontaneous pain responses that characterize the pain associated with toothache.

Purine biosynthesis in L1210 leukemia cells is inhibited by 7-hydroxymethotrexate (7-OH-MTX) polyglutamates (PGS)

International Nuclear Information System (INIS)

Seither, R.L.; Matherly, L.H.; Goldman, I.D.

1986-01-01

The biochemical basis for 7-OH-MTX cytotoxicity was examined in L1210 tumor cells. Cells were exposed to 100 μM 7-OH-MTX (approx. 50% growth inhibition) or 10 μM methotrexate (MTX) (approx. 95% growth inhibition) for 6 hrs to allow high levels of PGS to accumulate. Dihydrofolate reductase (DHFR) activity was assessed by dihydrofolate (FH 2 ) pools labeled with 5-formyl-[ 3 H]-tetrahydrofolate (5μM) or 3 H-folic acid (1 μM). FH 2 was not elevated above control levels in 7-OH-MTX treated cells, in contrast to MTX treated cells in which FH 2 increased 4- to 7-fold. 3 H-Deoxyuridine incorporation into DNA was not inhibited in cells containing high levels (11.5 nmol/g dry wt.) of 7-OH-MTX tetraglutamate (7-OH-4-NH 2 -10-CH 3 -PteGlu 4 ), well in excess of the DHFR-binding capacity (7.3 +/- 0.9 nmol/g), indicating a normal rate of thymidylate synthesis. Although small amounts of 7-OH-MTX and its PGS were bound to DHFR in L1210 cells, as assessed by gel filtration, there was evidence for the preferential binding of 7-OH-MTX tetraglutamate. In all cases this was well below the DHFR binding capacity, consistent with normal rates of deoxyuridine metabolism and FH 2 levels in the cell. Incorporation of 14 C-formate (60 min) into thymidylate and amino acids was unaffected by 7-OH-MTX, yet incorporation into purines was inhibited over 50%, supporting a block(s) in de novo purine biosynthesis

Bladder contractility is modulated by Kv7 channels in pig detrusor

DEFF Research Database (Denmark)

Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja

2013-01-01

Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view...... relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P...

AR-v7 protein expression is regulated by protein kinase and phosphatase

Science.gov (United States)

Li, Yinan; Xie, Ning; Gleave, Martin E.; Rennie, Paul S.; Dong, Xuesen

2015-01-01

Failure of androgen-targeted therapy and progression of castration-resistant prostate cancer (CRPC) are often attributed to sustained expression of the androgen receptor (AR) and its major splice variant, AR-v7. Although the new generation of anti-androgens such as enzalutamide effectively inhibits AR activity, accumulating pre-clinical and clinical evidence indicates that AR-v7 remains constitutively active in driving CRPC progression. However, molecular mechanisms which control AR-v7 protein expression remain unclear. We apply multiple prostate cancer cell models to demonstrate that enzalutamide induces differential activation of protein phosphatase-1 (PP-1) and Akt kinase depending on the gene context of cancer cells. The balance between PP-1 and Akt activation governs AR phosphorylation status and activation of the Mdm2 ubiquitin ligase. Mdm2 recognizes phosphorylated serine 213 of AR-v7, and induces AR-v7 ubiquitination and protein degradation. These findings highlight the decisive roles of PP-1 and Akt for AR-v7 protein expression and activities when AR is functionally blocked. PMID:26378044

Bone Morphogenetic Protein (BMP-7 expression is decreased in human hypertensive nephrosclerosis

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Cohen Clemens D

2010-11-01

Full Text Available Abstract Background Bone Morphogenetic Protein (BMP-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8 expression was quantified in proximal tubular cells (HK-2. Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-β induced epithelial-to-mesenchymal transition (EMT, expression of TGF-β receptor type I (TGF-βRI and phosphorylated Smad 2 (pSmad 2 as well as on TNF-α induced apoptosis of proximal tubular cells. Results BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml were able to reverse TNF-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2. Conclusions The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.

Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes

Science.gov (United States)

Bernerd, Francoise; Sarasin, Alain; Magnaldo, Thierry

1999-01-01

Galectin-7 is a β-galactoside binding protein specifically expressed in stratified epithelia and notably in epidermis, but barely detectable in epidermal tumors and absent from squamous carcinoma cell lines. Galectin-7 gene is an early transcriptional target of the tumor suppressor protein P53 [Polyak, K., Xia, Y., Zweier, J., Kinzler, K. & Vogelstein, B. (1997) Nature (London) 389, 300–305]. Because p53 transcriptional activity is increased by genotoxic stresses we have examined the possible effects of ultraviolet radiations (UVB) on galectin-7 expression in epidermal keratinocytes. The amounts of galectin-7 mRNA and protein are increased rapidly after UVB irradiation of epidermal keratinocytes. The increase of galectin-7 is parallel to P53 stabilization. UVB irradiation of skin reconstructed in vitro and of human skin ex vivo demonstrates that galectin-7 overexpression is associated with sunburn/apoptotic keratinocytes. Transfection of a galectin-7 expression vector results in a significant increase in terminal deoxynucleotidyltransferase-mediated UTP end labeling-positive keratinocytes. The present findings demonstrate a keratinocyte-specific protein involved in the UV-induced apoptosis, an essential process in the maintenance of epidermal homeostasis. PMID:10500176

The PTPN14 Tumor Suppressor Is a Degradation Target of Human Papillomavirus E7.

Science.gov (United States)

Szalmás, Anita; Tomaić, Vjekoslav; Basukala, Om; Massimi, Paola; Mittal, Suruchi; Kónya, József; Banks, Lawrence

2017-04-01

Activation of signaling pathways ensuring cell growth is essential for the proliferative competence of human papillomavirus (HPV)-infected cells. Tyrosine kinases and phosphatases are key regulators of cellular growth control pathways. A recently identified potential cellular target of HPV E7 is the cytoplasmic protein tyrosine phosphatase PTPN14, which is a potential tumor suppressor and is linked to the control of the Hippo and Wnt/beta-catenin signaling pathways. In this study, we show that the E7 proteins of both high-risk and low-risk mucosal HPV types can interact with PTPN14. This interaction is independent of retinoblastoma protein (pRb) and involves residues in the carboxy-terminal region of E7. We also show that high-risk E7 induces proteasome-mediated degradation of PTPN14 in cells derived from cervical tumors. This degradation appears to be independent of cullin-1 or cullin-2 but most likely involves the UBR4/p600 ubiquitin ligase. The degree to which E7 downregulates PTPN14 would suggest that this interaction is important for the viral life cycle and potentially also for the development of malignancy. In support of this we find that overexpression of PTPN14 decreases the ability of HPV-16 E7 to cooperate with activated EJ-ras in primary cell transformation assays. IMPORTANCE This study links HPV E7 to the deregulation of protein tyrosine phosphatase signaling pathways. PTPN14 is classified as a potential tumor suppressor protein, and here we show that it is very susceptible to HPV E7-induced proteasome-mediated degradation. Intriguingly, this appears to use a mechanism that is different from that employed by E7 to target pRb. Therefore, this study has important implications for our understanding of the molecular basis for E7 function and also sheds important light on the potential role of PTPN14 as a tumor suppressor. Copyright © 2017 American Society for Microbiology.

7 CFR 1486.100 - What is the Emerging Markets Program?

Science.gov (United States)

2010-01-01

... include activities such as feasibility studies, market research, sector assessments, orientation visits... intended primarily to support export market development efforts of the private sector, but the Program's... 7 Agriculture 10 2010-01-01 2010-01-01 false What is the Emerging Markets Program? 1486.100...

Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma

International Nuclear Information System (INIS)

Liang, Yu; Bollen, Andrew W; Aldape, Ken D; Gupta, Nalin

2006-01-01

We previously identified brain type fatty acid-binding protein (FABP7) as a prognostic marker for patients with glioblastoma (GBM). Increased expression of FABP7 is associated with reduced survival. To investigate possible molecular mechanisms underlying this association, we compared the expression and subcellular localization of FABP7 in non-tumor brain tissues with different types of glioma, and examined the expression of FABP7 and epidermal growth factor receptor (EGFR) in GBM tumors. Expression of FABP7 in non-tumor brain and glioma specimens was examined using immunohistochemistry, and its correlation to the clinical behavior of the tumors was analyzed. We also analyzed the association between FABP7 and EGFR expression in different sets of GBM specimens using published DNA microarray datasets and semi-quantitative immunohistochemistry. In vitro migration was examined using SF763 glioma cell line. FABP7 was present in a unique population of glia in normal human brain, and its expression was increased in a subset of reactive astrocytes. FABP7 immunoreactivity in grade I pilocytic astrocytoma was predominantly cytoplasmic, whereas nuclear FABP7 was detected in other types of infiltrative glioma. Nuclear, not cytoplasmic, FABP7 immunoreactivity was associated with EGFR overexpression in GBM (N = 61, p = 0.008). Expression of the FABP7 gene in GBM also correlated with the abundance of EGFR mRNA in our previous microarray analyses (N = 34, p = 0.016) and an independent public microarray dataset (N = 28, p = 0.03). Compared to those negative for both markers, nuclear FABP7-positive/EGFR-positive and nuclear FABP7-positive/EGFR-negative GBM tumors demonstrated shortest survival, whereas those only positive for EGFR had intermediate survival. EGFR activation increased nuclear FABP7 immunoreactivity in a glioma cell line in vitro, and inhibition of FABP7 expression suppressed EGF-induced glioma-cell migration. Our data suggested that in EGFR-positive GBM the presence of

HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype.

Science.gov (United States)

Monterisi, Simona; Lo Riso, Pietro; Russo, Karin; Bertalot, Giovanni; Vecchi, Manuela; Testa, Giuseppe; Di Fiore, Pier Paolo; Bianchi, Fabrizio

2018-03-26

HOXB7 is a homeodomain (HOX) transcription factor involved in regional body patterning of invertebrates and vertebrates. We previously identified HOXB7 within a ten-gene prognostic signature for lung adenocarcinoma, where increased expression of HOXB7 was associated with poor prognosis. This raises the question of how HOXB7 overexpression can influence the metastatic behavior of lung adenocarcinoma. Here, we analyzed publicly available microarray and RNA-seq lung cancer expression datasets and found that HOXB7-overexpressing tumors are enriched in gene signatures characterizing adult and embryonic stem cells (SC), and induced pluripotent stem cells (iPSC). Experimentally, we found that HOXB7 upregulates several canonical SC/iPSC markers and sustains the expansion of a subpopulation of cells with SC characteristics, through modulation of LIN28B, an emerging cancer gene and pluripotency factor, which we discovered to be a direct target of HOXB7. We validated this new circuit by showing that HOXB7 enhances reprogramming to iPSC with comparable efficiency to LIN28B or its target c-MYC, which is a canonical reprogramming factor.

Whi7 is an unstable cell-cycle repressor of the Start transcriptional program.

Science.gov (United States)

Gomar-Alba, Mercè; Méndez, Ester; Quilis, Inma; Bañó, M Carmen; Igual, J Carlos

2017-08-24

Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional program by G1 CDK-cyclin complexes through the inactivation of Start transcriptional repressors, Whi5 in yeast or Rb in mammals. Here we provide novel keys of how Whi7, a protein related at sequence level to Whi5, represses Start. Whi7 is an unstable protein, degraded by the SCF Grr1 ubiquitin-ligase, whose stability is cell cycle regulated by CDK1 phosphorylation. Importantly, Whi7 associates to G1/S gene promoters in late G1 acting as a repressor of SBF-dependent transcription. Our results demonstrate that Whi7 is a genuine paralog of Whi5. In fact, both proteins collaborate in Start repression bringing to light that yeast cells, as occurs in mammalian cells, rely on the combined action of multiple transcriptional repressors to block Start transition.The commitment of cells to a new cycle of division involves inactivation of the Start transcriptional repressor Whi5. Here the authors show that the sequence related protein Whi7 associates to G1/S gene promoters in late G1 and collaborates with Whi5 in Start repression.

Abnormal Uterine Bleeding Is Associated With Increased BMP7 Expression in Human Endometrium.

Science.gov (United States)

Richards, Elliott G; El-Nashar, Sherif A; Schoolmeester, John K; Keeney, Gary L; Mariani, Andrea; Hopkins, Matthew R; Dowdy, Sean C; Daftary, Gaurang S; Famuyide, Abimbola O

2017-05-01

Abnormal uterine bleeding (AUB), a common health concern of women, is a heterogeneous clinical entity that is traditionally categorized into organic and nonorganic causes. Despite varied pharmacologic treatments, few offer sustained efficacy, as most are empiric, unfocused, and do not directly address underlying dysregulated molecular mechanisms. Characterization of such molecular derangements affords the opportunity to develop and use novel, more successful treatments for AUB. Given its implication in other organ systems, we hypothesized that bone morphogenetic protein (BMP) expression is altered in patients with AUB and hence comprehensively investigated dysregulation of BMP signaling pathways by systematically screening 489 samples from 365 patients for differences in the expression of BMP2, 4, 6, and 7 ligands, BMPR1A and B receptors, and downstream SMAD4, 6, and 7 proteins. Expression analysis was correlated clinically with data abstracted from medical records, including bleeding history, age at procedure, ethnicity, body mass index, hormone treatment, and histological diagnosis of fibroids, polyps, adenomyosis, hyperplasia, and cancer. Expression of BMP7 ligand was significantly increased in patients with AUB (H-score: 18.0 vs 26.7; P bleeding (menorrhagia) as their specific AUB pattern demonstrated significantly higher BMP7 expression. Significantly, no differences in the expression of any other BMP ligands, receptors, or SMAD proteins were observed in this large patient cohort. However, expression of BMPR1A, BMPR1B, and SMAD4 was significantly decreased in cancer compared to benign samples. Our study demonstrates that BMP7 is a promising target for future investigation and pharmacologic treatment of AUB.

Variabilité selon le captureur de l'efficacité de répulsifs à base d'huiles végétales dans la protection individuelle contre les piqûres de Simulium damnosum s. l.

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Sylla M.

2002-12-01

Full Text Available Dans le présent article, nous faisons état de la variabilité selon le captureur de l'efficacité de répulsifs à base d'huiles végétales appliquées sur la peau contre les piqûres de Simulium damnosum s. l. Les expérimentations ont été effectuées en zones de savane (Chaussée-Niaka et de forêt (Soubré de Côte d'Ivoire. Les formulations (lotions, crèmes] testées lors de ces travaux ont été obtenues à partir d'huiles d'amande de palme (Elaeis guineensis, de coco (Cocos nucifera et de gobi (Carapa procera. La technique classique de capture sur homme à l'aide de tubes à hémolyse en matière plastique a été utilisée. Pour chaque journée d'expérimentation, un captureur non traité (jambes non enduites de répulsif servait de témoin. Les résultats indiquent qu'en savane, quels que soient le répulsif et le captureur, la densité simulidienne se situait de 1 à 4, 1 à 6 et de 2 à 10 simulies par homme et par jour lorsque le captureur était respectivement protégé avec le coco, le palmiste et le gobi. Avec les mêmes répulsifs, en zone de forêt, l'agressivité simulidienne variait de 9 à 16, de 2 à 30 et de 8 à 49 piqûres par jour. En comparaison, le témoin recevait de 67 à 90 et de 310 à 533 piqûres par jour, respectivement en zones de savane et de forêt. Malgré les variations importantes dans le nombre de simulies capturées en fonction du captureur choisi, nos résultats montrent que quels que soient le répulsif et l'espèce simulidienne, une protection similaire est conférée à tous les captureurs. Ils indiquent également que le recours à des substances naturelles locales, utilisées comme répulsifs en application dermique, est l'une des meilleures méthodes de protection personnelle contre les simulies.

Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer

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Zheng, Jun; Zhang, Ding; Liu, Wei; Zheng, Wei Hong; Li, Xiao Song; Yao, Ru Cheng; Wang, Fangyu; Liu, Sen; Tan, Xiao

2018-01-01

Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease. PMID:29560118

Regulator of G Protein Signaling 7 (RGS7) Can Exist in a Homo-oligomeric Form That Is Regulated by Gαo and R7-binding Protein.

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Tayou, Junior; Wang, Qiang; Jang, Geeng-Fu; Pronin, Alexey N; Orlandi, Cesare; Martemyanov, Kirill A; Crabb, John W; Slepak, Vladlen Z

2016-04-22

RGS (regulator of G protein signaling) proteins of the R7 subfamily (RGS6, -7, -9, and -11) are highly expressed in neurons where they regulate many physiological processes. R7 RGS proteins contain several distinct domains and form obligatory dimers with the atypical Gβ subunit, Gβ5 They also interact with other proteins such as R7-binding protein, R9-anchoring protein, and the orphan receptors GPR158 and GPR179. These interactions facilitate plasma membrane targeting and stability of R7 proteins and modulate their activity. Here, we investigated RGS7 complexes using in situ chemical cross-linking. We found that in mouse brain and transfected cells cross-linking causes formation of distinct RGS7 complexes. One of the products had the apparent molecular mass of ∼150 kDa on SDS-PAGE and did not contain Gβ5 Mass spectrometry analysis showed no other proteins to be present within the 150-kDa complex in the amount close to stoichiometric with RGS7. This finding suggested that RGS7 could form a homo-oligomer. Indeed, co-immunoprecipitation of differentially tagged RGS7 constructs, with or without chemical cross-linking, demonstrated RGS7 self-association. RGS7-RGS7 interaction required the DEP domain but not the RGS and DHEX domains or the Gβ5 subunit. Using transfected cells and knock-out mice, we demonstrated that R7-binding protein had a strong inhibitory effect on homo-oligomerization of RGS7. In contrast, our data indicated that GPR158 could bind to the RGS7 homo-oligomer without causing its dissociation. Co-expression of constitutively active Gαo prevented the RGS7-RGS7 interaction. These results reveal the existence of RGS protein homo-oligomers and show regulation of their assembly by R7 RGS-binding partners. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Is there a link between proprotein convertase PC7 activity and human lipid homeostasis?

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Johann Guillemot

2014-01-01

Full Text Available A genome-wide association study suggested that a R504H mutation in the proprotein convertase PC7 is associated with increased circulating levels of HDL and reduced triglycerides in black Africans. Our present results show that PC7 and PC7-R504H exhibit similar processing of transferrin receptor-1, proSortilin, and apolipoprotein-F. Plasma analyses revealed no change in the lipid profiles, insulin or glucose of wild type and PC7 KO mice. Thus, the R504H mutation does not modify the proteolytic activity of PC7. The mechanisms behind the implication of PC7 in the regulation of human HDL, triglycerides and in modifying the levels of atherogenic small dense LDL remain to be elucidated.

World health day - 7th april, 2004 "road safety is no accident"

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S C Saxena

2004-06-01

Full Text Available In 1948, the First World Health Assembly called for the creation of a "World Health Day". Since 1950, World Health Day has been celebrated on the 7th of April of each year. The objective of World Health Day is to raise global awareness of a specific health theme to highlight a priority area of concern for the World Health Organization (WHO. The Day serves as a launch for a long-term advocacy program for which activities will be undertaken and resources provided well beyond 7th April. To Celebrate the theme of this year "Road Safety is No accident", on 7th April 2004 around the globle, hundreds of organizations hosted events to help raise awareness about road traffic injuries, their grave consequences and enormous casts to society. They also contributed to spreading the message that such injuries can be prevented. In 1948, the First World Health Assembly called for the creation of a "World Health Day". Since 1950, World Health Day has been celebrated on the 7th of April of each year. The objective of World Health Day is to raise global awareness of a specific health theme to highlight a priority area of concern for the World Health Organization (WHO. The Day serves as a launch for a long-term advocacy program for which activities will be undertaken and resources provided well beyond 7th April. To Celebrate the theme of this year "Road Safety is No accident", on 7th April 2004 around the globle, hundreds of organizations hosted events to help raise awareness about road traffic injuries, their grave consequences and enormous casts to society. They also contributed to spreading the message that such injuries can be prevented. The accident is defined as unexpected, unplanned event envolving injury, disability or death. The accidents occur in almost all countries. The most alarming fact is that accidents kill more young trained adults between 15-24 years of age group of males, mainly among two wheelers. All sorts of accidents kill more than 5 million

World health day - 7th april, 2004 "road safety is no accident"

Directory of Open Access Journals (Sweden)

S C Saxena

2006-06-01

Full Text Available In 1948, the First World Health Assembly called for the creation of a "World Health Day". Since 1950, World Health Day has been celebrated on the 7th of April of each year. The objective of World Health Day is to raise global awareness of a specific health theme to highlight a priority area of concern for the World Health Organization (WHO. The Day serves as a launch for a long-term advocacy program for which activities will be undertaken and resources provided well beyond 7th April.To Celebrate the theme of this year "Road Safety is No accident", on 7th April 2004 around the globle, hundreds of organizations hosted events to help raise awareness about road traffic injuries, their grave consequences and enormous casts to society. They alsocontributed to spreading the message that such injuries can be prevented.In 1948, the First World Health Assembly called for the creation of a "World Health Day". Since 1950, World Health Day has been celebrated on the 7th of April of each year. The objective of World Health Day is to raise global awareness of a specific health theme to highlight a priority area of concern for the World Health Organization (WHO. The Day serves as a launch for a long-term advocacy program for which activities will be undertaken and resources provided well beyond 7th April.To Celebrate the theme of this year "Road Safety is No accident", on 7th April 2004 around the globle, hundreds of organizations hosted events to help raise awareness about road traffic injuries, their grave consequences and enormous casts to society. They alsocontributed to spreading the message that such injuries can be prevented.t '            ■The accident is defined as unexpected, unplanned event envolving injury, disability or death. The accidents occur in almost all countries. The most alarming fact is that accidents kill more young trained adults between 15-24 years of age group of males, mainly among two wheelers. All sorts of accidents

A novel gene THSD7A is associated with obesity.

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Nizamuddin, S; Govindaraj, P; Saxena, S; Kashyap, M; Mishra, A; Singh, S; Rotti, H; Raval, R; Nayak, J; Bhat, B K; Prasanna, B V; Dhumal, V R; Bhale, S; Joshi, K S; Dedge, A P; Bharadwaj, R; Gangadharan, G G; Nair, S; Gopinath, P M; Patwardhan, B; Kondaiah, P; Satyamoorthy, K; Valiathan, M S; Thangaraj, K

2015-11-01

Body mass index (BMI) is a non-invasive measurement of obesity. It is commonly used for assessing adiposity and obesity-related risk prediction. Genetic differences between ethnic groups are important factors, which contribute to the variation in phenotypic effects. India inhabited by the first out-of-Africa human population and the contemporary Indian populations are admixture of two ancestral populations; ancestral north Indians (ANI) and ancestral south Indians (ASI). Although ANI are related to Europeans, ASI are not related to any group outside Indian-subcontinent. Hence, we expect novel genetic loci associated with BMI. In association analysis, we found eight genic SNPs in extreme of distribution (P⩽3.75 × 10(-5)), of which WWOX has already been reported to be associated with obesity-related traits hence excluded from further study. Interestingly, we observed rs1526538, an intronic SNP of THSD7A; a novel gene significantly associated with obesity (P=2.88 × 10(-5), 8.922 × 10(-6) and 2.504 × 10(-9) in discovery, replication and combined stages, respectively). THSD7A is neural N-glycoprotein, which promotes angiogenesis and it is well known that angiogenesis modulates obesity, adipose metabolism and insulin sensitivity, hence our result find a correlation. This information can be used for drug target, early diagnosis of obesity and treatment.

Cdc7 is required throughout the yeast S phase to activate replication origins.

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Donaldson, A D; Fangman, W L; Brewer, B J

1998-02-15

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.

A radial glia gene marker, fatty acid binding protein 7 (FABP7, is involved in proliferation and invasion of glioblastoma cells.

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Antonella De Rosa

Full Text Available Glioblastoma multiforme (GBM is among the most deadly cancers. A number of studies suggest that a fraction of tumor cells with stem cell features (Glioma Stem-like Cells, GSC might be responsible for GBM recurrence and aggressiveness. GSC similarly to normal neural stem cells, can form neurospheres (NS in vitro, and seem to mirror the genetic features of the original tumor better than glioma cells growing adherently in the presence of serum. Using cDNA microarray analysis we identified a number of relevant genes for glioma biology that are differentially expressed in adherent cells and neurospheres derived from the same tumor. Fatty acid-binding protein 7 (FABP7 was identified as one of the most highly expressed genes in NS compared to their adherent counterpart. We found that down-regulation of FABP7 expression in NS by small interfering RNAs significantly reduced cell proliferation and migration. We also evaluated the potential involvement of FABP7 in response to radiotherapy, as this treatment may cause increased tumor infiltration. Migration of irradiated NS was associated to increased expression of FABP7. In agreement with this, in vivo reduced tumorigenicity of GBM cells with down-regulated expression of FABP7 was associated to decreased expression of the migration marker doublecortin. Notably, we observed that PPAR antagonists affect FABP7 expression and decrease the migration capability of NS after irradiation. As a whole, the data emphasize the role of FABP7 expression in GBM migration and provide translational hints on the timing of treatment with anti-FABP7 agents like PPAR antagonists during GBM evolution.

Synaptotagmin-7 is an asynchronous calcium sensor for synaptic transmission in neurons expressing SNAP-23.

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Jens P Weber

Full Text Available Synchronization of neurotransmitter release with the presynaptic action potential is essential for maintaining fidelity of information transfer in the central nervous system. However, synchronous release is frequently accompanied by an asynchronous release component that builds up during repetitive stimulation, and can even play a dominant role in some synapses. Here, we show that substitution of SNAP-23 for SNAP-25 in mouse autaptic glutamatergic hippocampal neurons results in asynchronous release and a higher frequency of spontaneous release events (mEPSCs. Use of neurons from double-knock-out (SNAP-25, synaptotagmin-7 mice in combination with viral transduction showed that SNAP-23-driven release is triggered by endogenous synaptotagmin-7. In the absence of synaptotagmin-7 release became even more asynchronous, and the spontaneous release rate increased even more, indicating that synaptotagmin-7 acts to synchronize release and suppress spontaneous release. However, compared to synaptotagmin-1, synaptotagmin-7 is a both leaky and asynchronous calcium sensor. In the presence of SNAP-25, consequences of the elimination of synaptotagmin-7 were small or absent, indicating that the protein pairs SNAP-25/synaptotagmin-1 and SNAP-23/synaptotagmin-7 might act as mutually exclusive calcium sensors. Expression of fusion proteins between pHluorin (pH-sensitive GFP and synaptotagmin-1 or -7 showed that vesicles that fuse using the SNAP-23/synaptotagmin-7 combination contained synaptotagmin-1, while synaptotagmin-7 barely displayed activity-dependent trafficking between vesicle and plasma membrane, implying that it acts as a plasma membrane calcium sensor. Overall, these findings support the idea of alternative syt∶SNARE combinations driving release with different kinetics and fidelity.

Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory.

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Lazaroni, Thiago L N; Raslan, Ana Cláudia S; Fontes, Walkiria R P; de Oliveira, Marilene L; Bader, Michael; Alenina, Natalia; Moraes, Márcio F D; Dos Santos, Robson A; Pereira, Grace S

2012-01-01

It has been shown that the brain has its own intrinsic renin-angiotensin system (RAS) and angiotensin-(1-7) (Ang-(1-7)) is particularly interesting, because it appears to counterbalance most of the Ang II effects. Ang-(1-7) exerts its biological function through activation of the G-protein-coupled receptor Mas. Interestingly, hippocampus is one of the regions with higher expression of Mas. However, the role of Ang-(1-7)/Mas axis in hippocampus-dependent memories is still poorly understood. Here we demonstrated that Mas ablation, as well as the blockade of Mas in the CA1-hippocampus, impaired object recognition memory (ORM). We also demonstrated that the blockade of Ang II receptors AT1, but not AT2, recovers ORM impairment of Mas-deficient mice. Considering that high concentrations of Ang-(1-7) may activate AT1 receptors, nonspecifically, we evaluate the levels of Ang-(1-7) and its main precursors Ang I and Ang II in the hippocampus of Mas-deficient mice. The Ang I and Ang II levels are unaltered in the whole hipocampus of MasKo. However, Ang-(1-7) concentration is increased in the whole hippocampus of MasKo mice, as well as in the CA1 area. Taken together, our findings suggest that the functionality of the Ang-(1-7)/Mas axis is essential for normal ORM processing. Copyright © 2011 Elsevier Inc. All rights reserved.

Oct4 is required ~E7.5 for proliferation in the primitive streak.

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Brian DeVeale

2013-11-01

Full Text Available Oct4 is a widely recognized pluripotency factor as it maintains Embryonic Stem (ES cells in a pluripotent state, and, in vivo, prevents the inner cell mass (ICM in murine embryos from differentiating into trophectoderm. However, its function in somatic tissue after this developmental stage is not well characterized. Using a tamoxifen-inducible Cre recombinase and floxed alleles of Oct4, we investigated the effect of depleting Oct4 in mouse embryos between the pre-streak and headfold stages, ~E6.0-E8.0, when Oct4 is found in dynamic patterns throughout the embryonic compartment of the mouse egg cylinder. We found that depletion of Oct4 ~E7.5 resulted in a severe phenotype, comprised of craniorachischisis, random heart tube orientation, failed turning, defective somitogenesis and posterior truncation. Unlike in ES cells, depletion of the pluripotency factors Sox2 and Oct4 after E7.0 does not phenocopy, suggesting that ~E7.5 Oct4 is required within a network that is altered relative to the pluripotency network. Oct4 is not required in extraembryonic tissue for these processes, but is required to maintain cell viability in the embryo and normal proliferation within the primitive streak. Impaired expansion of the primitive streak occurs coincident with Oct4 depletion ∼E7.5 and precedes deficient convergent extension which contributes to several aspects of the phenotype.

ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

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Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: tangmengxiongsdu8@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)

2013-08-15

Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

International Nuclear Information System (INIS)

Zhang, Wenchao; Wang, Hui; Zhang, Wei; Lv, Ruijuan; Wang, Zhihao; Shang, Yuanyuan; Zhang, Yun; Zhong, Ming; Chen, Yuguo; Tang, Mengxiong

2013-01-01

Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients

Ck2-Dependent Phosphorylation Is Required to Maintain Pax7 Protein Levels in Proliferating Muscle Progenitors.

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Natalia González

Full Text Available Skeletal muscle regeneration and long term maintenance is directly link to the balance between self-renewal and differentiation of resident adult stem cells known as satellite cells. In turn, satellite cell fate is influenced by a functional interaction between the transcription factor Pax7 and members of the MyoD family of muscle regulatory factors. Thus, changes in the Pax7-to-MyoD protein ratio may act as a molecular rheostat fine-tuning acquisition of lineage identity while preventing precocious terminal differentiation. Pax7 is expressed in quiescent and proliferating satellite cells, while its levels decrease sharply in differentiating progenitors Pax7 is maintained in cells (reacquiring quiescence. While the mechanisms regulating Pax7 levels based on differentiation status are not well understood, we have recently described that Pax7 levels are directly regulated by the ubiquitin-ligase Nedd4, thus promoting proteasome-dependent Pax7 degradation in differentiating satellite cells. Here we show that Pax7 levels are maintained in proliferating muscle progenitors by a mechanism involving casein kinase 2-dependent Pax7 phosphorylation at S201. Point mutations preventing S201 phosphorylation or casein kinase 2 inhibition result in decreased Pax7 protein in proliferating muscle progenitors. Accordingly, this correlates directly with increased Pax7 ubiquitination. Finally, Pax7 down regulation induced by casein kinase 2 inhibition results in precocious myogenic induction, indicating early commitment to terminal differentiation. These observations highlight the critical role of post translational regulation of Pax7 as a molecular switch controlling muscle progenitor fate.

PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement.

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Silvia Gärtner

Full Text Available Protein Tyrosin Kinase 7 (PTK7 is upregulated in several human cancers; however, its clinical implication in breast cancer (BC and lymph node (LN is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033 in BC and nodal involvement (ANOVA, p = 0.007 in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041. Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance.

PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement.

Science.gov (United States)

Gärtner, Silvia; Gunesch, Angela; Knyazeva, Tatiana; Wolf, Petra; Högel, Bernhard; Eiermann, Wolfgang; Ullrich, Axel; Knyazev, Pjotr; Ataseven, Beyhan

2014-01-01

Protein Tyrosin Kinase 7 (PTK7) is upregulated in several human cancers; however, its clinical implication in breast cancer (BC) and lymph node (LN) is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC) cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033) in BC and nodal involvement (ANOVA, p = 0.007) in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041). Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance.

Cardiovascular Small Heat Shock Protein HSPB7 Is a Kinetically Privileged Reactive Electrophilic Species (RES) Sensor.

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Surya, Sanjna L; Long, Marcus J C; Urul, Daniel A; Zhao, Yi; Mercer, Emily J; EIsaid, Islam M; Evans, Todd; Aye, Yimon

2018-02-08

Small heat shock protein (sHSP)-B7 (HSPB7) is a muscle-specific member of the non-ATP-dependent sHSPs. The precise role of HSPB7 is enigmatic. Here, we disclose that zebrafish Hspb7 is a kinetically privileged sensor that is able to react rapidly with native reactive electrophilic species (RES), when only substoichiometric amounts of RES are available in proximity to Hspb7 expressed in living cells. Among the two Hspb7-cysteines, this RES sensing is fulfilled by a single cysteine (C117). Purification and characterizations in vitro reveal that the rate for RES adduction is among the most efficient reported for protein-cysteines with native carbonyl-based RES. Covalent-ligand binding is accompanied by structural changes (increase in β-sheet-content), based on circular dichroism analysis. Among the two cysteines, only C117 is conserved across vertebrates; we show that the human ortholog is also capable of RES sensing in cells. Furthermore, a cancer-relevant missense mutation reduces this RES-sensing property. This evolutionarily conserved cysteine-biosensor may play a redox-regulatory role in cardioprotection.

Biting-density and microfilariae infection of Simulium damnosum ...

African Journals Online (AJOL)

Investigations on the biting-density and microfilariae infection rate of S. damnosumsl population caught around the Mada River was conducted between May 2013 to April 2014. Captured flies were morphologically identified and dissected for parity and infectivity rate. A total of 308 adult female S. damnosum sl were caught, ...

Fbxw7-associated drug resistance is reversed by induction of terminal differentiation in murine intestinal organoid culture

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Federica Lorenzi

2016-01-01

Full Text Available Colorectal cancer (CRC is one of the top three cancer-related causes of death worldwide. FBXW7 is a known tumor-suppressor gene, commonly mutated in CRC and in a variety of other epithelial tumors. Low expression of FBXW7 is also associated with poor prognosis. Loss of FBXW7 sensitizes cancer cells to certain drugs, while making them more resistant to other types of chemotherapies. However, is not fully understood how epithelial cells within normal gut and primary tumors respond to potential cancer therapeutics. We have studied genetically engineered mice in which the fbxw7 gene is conditionally knocked-out in the intestine (fbxw7ΔG. To further investigate the mechanism of Fbxw7-action, we grew intestinal crypts from floxed-fbxw7 (fbxw7fl/fl and fbxw7ΔG mice, in a Matrigel-based organoid (mini-gut culture. The fbxw7ΔG organoids exhibited rapid budding events in the crypt region. Furthermore, to test organoids for drug response, we exposed day 3 intestinal organoids from fbxw7fl/fl and fbxw7ΔG mice, to various concentrations of 5-fluorouracil (5-FU for 72 hours. 5-FU triggers phenotypic differences in organoids including changing shape, survival, resistance, and death. 5-FU however, rescues the drug-resistance phenotype of fbxw7ΔG through the induction of terminal differentiation. Our results support the hypothesis that a differentiating therapy successfully targets FBXW7-mutated CRC cells.

Variation in density of cattle-visiting muscid flies between Danish inland pastures

DEFF Research Database (Denmark)

Jensen, Karl-Martin Vagn; Jespersen, Jørgen B.; Nielsen, B. Overgaard

1993-01-01

The density of cattle-visiting flies (Muscidae) and the load of black-flies (Simulium spp.) were estimated in twelve and eighteen inland pastures in Denmark in 1984 and 1985 respectively. No differences in the geographical distribution pattern of the predominant cattle-visiting Muscidae were reco......-exposed pastures. A comparable relationship was found for Haematobia irritans. With Haematobosca stimulans (Mg.) and Morellia spp. no relation between grassland environment and fly density was detected....

Iron deficiency regulated OsOPT7 is essential for iron homeostasis in rice.

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Bashir, Khurram; Ishimaru, Yasuhiro; Itai, Reiko Nakanishi; Senoura, Takeshi; Takahashi, Michiko; An, Gynheung; Oikawa, Takaya; Ueda, Minoru; Sato, Aiko; Uozumi, Nobuyuki; Nakanishi, Hiromi; Nishizawa, Naoko K

2015-05-01

The molecular mechanism of iron (Fe) uptake and transport in plants are well-characterized; however, many components of Fe homeostasis remain unclear. We cloned iron-deficiency-regulated oligopeptide transporter 7 (OsOPT7) from rice. OsOPT7 localized to the plasma membrane and did not transport Fe(III)-DMA or Fe(II)-NA and GSH in Xenopus laevis oocytes. Furthermore OsOPT7 did not complement the growth of yeast fet3fet4 mutant. OsOPT7 was specifically upregulated in response to Fe-deficiency. Promoter GUS analysis revealed that OsOPT7 expresses in root tips, root vascular tissue and shoots as well as during seed development. Microarray analysis of OsOPT7 knockout 1 (opt7-1) revealed the upregulation of Fe-deficiency-responsive genes in plants grown under Fe-sufficient conditions, despite the high Fe and ferritin concentrations in shoot tissue indicating that Fe may not be available for physiological functions. Plants overexpressing OsOPT7 do not exhibit any phenotype and do not accumulate more Fe compared to wild type plants. These results indicate that OsOPT7 may be involved in Fe transport in rice.

Cholesterol 7alpha-hydroxylase (CYP7A1) activity is modified after chronic ingestion of depleted uranium in the rat.

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Racine, R; Grandcolas, L; Grison, S; Stefani, J; Delissen, O; Gourmelon, P; Veyssière, G; Souidi, M

2010-05-01

Depleted uranium (DU) is a radioactive heavy metal derived from the nuclear energy production. Its wide use in civilian and military items increases the risk of its environmental dissemination, and thus the risk of internal contamination of populations living in such contaminated territories. Previous studies have shown that vitamin D and cerebral cholesterol metabolisms were affected following chronic ingestion of DU. Even more than the brain, the liver is a crucial organ in cholesterol homeostasis since it regulates cholesterol distribution and elimination at body level. The aim of this work was to assess the impact of a low-level chronic ingestion of DU on hepatic cholesterol metabolism. Rats were contaminated with DU in their drinking water at a concentration of 40mg/l for 9 months. The major effect induced by DU was a decrease of CYP7A1 specific activity (-60%) correlated with a matching decrease of its product 7alpha-hydroxycholesterol in the plasma. Hepatic gene expression of transporters ABC A1, ABC G5, ABC G8 and of nuclear receptor RXR was increased, whereas that of catabolism enzyme CYP7B1 was decreased. Thus, after a chronic ingestion of DU, rats experience a modulation of cholesterol catabolism but overcome it, since their cholesterolemia is preserved and no pathology is declared.

MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis

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Yasmina Bauer

2017-03-01

Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease. Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7, Fas death receptor ligand, osteopontin and procollagen type I C-peptide, to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4. MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.

Expression of solute carrier 7A4 (SLC7A4) in the plasma membrane is not sufficient to mediate amino acid transport activity.

OpenAIRE

Wolf, Sabine; Janzen, Annette; Vékony, Nicole; Martiné, Ursula; Strand, Dennis; Closs, Ellen I

2002-01-01

Member 4 of human solute carrier family 7 (SLC7A4) exhibits significant sequence homology with the SLC7 subfamily of human cationic amino acid transporters (hCATs) [Sperandeo, Borsani, Incerti, Zollo, Rossi, Zuffardi, Castaldo, Taglialatela, Andria and Sebastio (1998) Genomics 49, 230-236]. It is therefore often referred to as hCAT-4 even though no convincing transport activity has been shown for this protein. We expressed SLC7A4 in Xenopus laevis oocytes, but could not detect any transport a...

PDE7B is involved in nandrolone decanoate hydrolysis in liver cytosol and its transcription is up-regulated by androgens in HepG2

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Emmanuel eStrahm

2014-05-01

Full Text Available Most androgenic drugs are available as esters for a prolonged depot action. However the enzymes involved in the hydrolysis of the esters have not been identified. There is one study indicating that PDE7B may be involved in the activation of testosterone enanthate. The aims are to identify the cellular compartments where the hydrolysis of testosterone enanthate and nandrolone decanoate occurs, and to investigate the involvement of PDE7B in the activation. We also determined if testosterone and nandrolone affect the expression of the PDE7B gene. The hydrolysis studies were performed in isolated human liver cytosolic and microsomal preparations with and without specific PDE7B inhibitor. The gene expression was studied in human hepatoma cells (HepG2 exposed to testosterone and nandrolone. We show that PDE7B serves as a catalyst of the hydrolysis of testosterone enanthate and nandrolone decanoate in liver cytosol. The gene expression of PDE7B was significantly induced 3- and 5- fold after 2 hours exposure to 1 µM testosterone enanthate and nandrolone decanoate, respectively. These results show that PDE7B is involved in the activation of esterified nandrolone and testosterone and that the gene expression of PDE7B is induced by supra-physiological concentrations of androgenic drugs.

Epidermal growth factor-like domain 7 is a marker of the endothelial lineage and active angiogenesis.

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Bambino, Kathryn; Lacko, Lauretta A; Hajjar, Katherine A; Stuhlmann, Heidi

2014-07-01

Epidermal growth factor-like domain 7 (Egfl7) expression in the developing embryo is largely restricted to sites of mesodermal progenitors of angioblasts/hemangioblasts and the vascular endothelium. We hypothesize that Egfl7 marks the endothelial lineage during embryonic development, and can be used to define the emergence of endothelial progenitor cells, as well as to visualize newly-forming vasculature in the embryo and during the processes of physiologic and pathologic angiogenesis in the adult. We have generated a transgenic mouse strain that expresses enhanced green fluorescent protein (eGFP) under the control of a minimal Egfl7 regulatory sequence (Egfl7:eGFP). Expression of the transgene recapitulated that of endogenous Egfl7 at sites of vasculogenesis and angiogenesis in the allantois, yolk sac, and in the embryo proper. The transgene was not expressed in the quiescent endothelium of most adult organs. However, the uterus and ovary, which undergo vascular growth and remodeling throughout the estrus cycle, expressed high levels of Egfl7:eGFP. Importantly, expression of the Egfl7:eGFP transgene was induced in adult neovasculature. We also found that increased Egfl7 expression contributed to pathologic revascularization in the mouse retina. To our knowledge, this is the first mouse model that enables monitoring of endothelial cells at sites of active vasculogenesis and angiogenesis. This model also facilitated the isolation and characterization of EGFL7(+) endothelial cell populations by fluorescence activated cell sorting (FACS). Together, our results demonstrate that the Egfl7:eGFP reporter mouse is a valuable tool that can be used to elucidate the mechanisms by which blood vessels form during development and under pathologic circumstances. © 2014 Wiley Periodicals, Inc.

Growth of the Developing Cerebral Cortex Is Controlled by MicroRNA-7 through the p53 Pathway

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Andrew Pollock

2014-05-01

Full Text Available Proper growth of the mammalian cerebral cortex is crucial for normal brain functions and is controlled by precise gene-expression regulation. Here, we show that microRNA-7 (miR-7 is highly expressed in cortical neural progenitors and describe miR-7 sponge transgenic mice in which miR-7-silencing activity is specifically knocked down in the embryonic cortex. Blocking miR-7 function causes microcephaly-like brain defects due to reduced intermediate progenitor (IP production and apoptosis. Upregulation of miR-7 target genes, including those implicated in the p53 pathway, such as Ak1 and Cdkn1a (p21, is responsible for abnormalities in neural progenitors. Furthermore, ectopic expression of Ak1 or p21 and specific blockade of miR-7 binding sites in target genes using protectors in vivo induce similarly reduced IP production. Using conditional miRNA sponge transgenic approaches, we uncovered an unexpected role for miR-7 in cortical growth through its interactions with genes in the p53 pathway.

Interruption of Onchocerca volvulus transmission in Northern Venezuela.

Science.gov (United States)

Convit, Jacinto; Schuler, Harland; Borges, Rafael; Olivero, Vimerca; Domínguez-Vázquez, Alfredo; Frontado, Hortencia; Grillet, María E

2013-10-07

Onchocerciasis is caused by Onchocerca volvulus and transmitted by Simulium species (black flies). In the Americas, the infection has been previously described in 13 discrete regional foci distributed among six countries (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela) where more than 370,000 people are currently considered at risk. Since 2001, disease control in Venezuela has relied on the mass drug administration to the at-risk communities. This report provides empirical evidence of interruption of Onchocerca volvulus transmission by Simulium metallicum in 510 endemic communities from two Northern foci of Venezuela, after 10-12 years of 6-monthly Mectizan (ivermectin) treatment to all the eligible residents. In-depth entomologic and epidemiologic surveys were serially conducted from 2001-2012 in selected (sentinel and extra-sentinel) communities from the North-central (NC) and North-east (NE) onchocerciasis foci of Venezuela in order to monitor the impact of ivermectin treatment. From 2007-2009, entomological indicators in both foci confirmed that 0 out of 112,637 S. metallicum females examined by PCR contained L3 infection in insect heads. The upper bound of the 95% confidence intervals of the infective rate of the vector reached values below 1% by 2009 (NC) and 2012 (NE). Additionally, after 14 (NC) and 22 (NE) rounds of treatment, the seasonal transmission potential (±UL CIs) of S. metallicum was under the critical threshold of 20 L3 per person per season. Serological analysis in school children Venezuela.

B7-H3 is a potent inhibitor of human T cell activation: No evidence for B7-H3 and TREML2 interaction

Science.gov (United States)

Leitner, Judith; Klauser, Christoph; Pickl, Winfried F.; Stöckl, Johannes; Majdic, Otto; Bardet, Anaïs F.; Kreil, David P.; Dong, Chen; Yamazaki, Tomohide; Zlabinger, Gerhard; Pfistershammer, Katharina; Steinberger, Peter

2010-01-01

B7-H3 belongs to the B7 superfamily, a group of molecules that costimulate or down-modulate T cell responses. Although it was shown that B7-H3 can inhibit T cell responses, several studies - most of them performed in murine systems - found B7-H3 to act in a costimulatory manner. In this study we have specifically addressed a potential functional dualism of human B7-H3 by assessing the effect of this molecule under varying experimental conditions as well as on different T cell subsets. We show that B7-H3 does not costimulate human T cells. In presence of strong activating signals, B7-H3 potently and consistently down-modulated human T cell responses. This inhibitory effect was evident when analyzing proliferation and cytokine production and affected naïve as well as pre-activated T cells. We furthermore demonstrate that B7-H3 - T cell interaction is characterized by an early suppression of IL-2 and that T cell inhibition can be reverted by exogenous IL-2. Since TREML2 has been recently described as costimulatory receptor of murine B7-H3 we have extensively analysed interaction of human B7-H3 with TREML2 (TLT2). In these experiments we found no evidence for such an interaction. Furthermore our data do not point to a role for murine TREML2 as a receptor for murine B7-H3. PMID:19544488

The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria

Energy Technology Data Exchange (ETDEWEB)

Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P.; Yi, Ling; Kaler, Stephen G.; Lutsenko, Svetlana; Ralle, Martina

2016-05-16

Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia).

Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock

Science.gov (United States)

Bessho, Yasumasa; Hirata, Hiromi; Masamizu, Yoshito; Kageyama, Ryoichiro

2003-01-01

Hes7, a bHLH gene essential for somitogenesis, displays cyclic expression of mRNA in the presomitic mesoderm (PSM). Here, we show that Hes7 protein is also expressed in a dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed that Hes7 and Lunatic fringe (Lfng) transcription occurs in the Hes7 protein-negative domains. Furthermore, Hes7 and Lfng transcription is constitutively up-regulated in the absence of Hes7 protein and down-regulated by stabilization of Hes7 protein. Thus, periodic repression by Hes7 protein is critical for the cyclic transcription of Hes7 and Lfng, and this negative feedback represents a molecular basis for the segmentation clock. PMID:12783854

7 CFR 1486.511 - What is the general policy regarding ethical conduct?

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false What is the general policy regarding ethical conduct...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS EMERGING... ethical conduct? (a) The Recipient shall maintain written standards of conduct governing the performance...

15 CFR 10.7 - Procedure when a recommended standard is not supported by a consensus.

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2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Procedure when a recommended standard is not supported by a consensus. 10.7 Section 10.7 Commerce and Foreign Trade Office of the Secretary... recommended standard is not supported by a consensus. If the Department determines that a recommended standard...

Sirtuin 7 is decreased in pulmonary fibrosis and regulates the fibrotic phenotype of lung fibroblasts.

Science.gov (United States)

Wyman, Anne E; Noor, Zahid; Fishelevich, Rita; Lockatell, Virginia; Shah, Nirav G; Todd, Nevins W; Atamas, Sergei P

2017-06-01

Pulmonary fibrosis is a severe condition with no cure and limited therapeutic options. A better understanding of its pathophysiology is needed. Recent studies have suggested that pulmonary fibrosis may be driven by accelerated aging-related mechanisms. Sirtuins (SIRTs), particularly SIRT1, SIRT3, and SIRT6, are well-known mediators of aging; however, limited data exist on the contribution of sirtuins to lung fibrosis. We assessed the mRNA and protein levels of all seven known sirtuins in primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in comparison with lung fibroblasts from healthy controls. These unbiased tests revealed a tendency for all sirtuins to be expressed at lower levels in fibroblasts from patients compared with controls, but the greatest decrease was observed with SIRT7. Similarly, SIRT7 was decreased in lung tissues of bleomycin-challenged mice. Inhibition of SIRT7 with siRNA in cultured lung fibroblasts resulted in an increase in collagen and α-smooth muscle actin (α-SMA). Reciprocally, overexpression of SIRT7 resulted in lower basal and TGF-β-induced levels of COL1A1, COL1A2, COL3A1, and α-SMA mRNAs, as well as collagen and α-SMA proteins. Induced changes in SIRT7 had no effect on endogenous TGF-β mRNA levels or latent TGF-β activation, but overexpression of SIRT7 reduced the levels of Smad3 mRNA and protein. In conclusion, the decline in SIRT7 in lung fibroblasts has a profibrotic effect, which is mediated by changes in Smad3 levels.

Let-7a is a direct EWS-FLI-1 target implicated in Ewing's sarcoma development.

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Claudio De Vito

Full Text Available Ewing's sarcoma family tumors (ESFT are the second most common bone malignancy in children and young adults, characterized by unique chromosomal translocations that in 85% of cases lead to expression of the EWS-FLI-1 fusion protein. EWS-FLI-1 functions as an aberrant transcription factor that can both induce and suppress members of its target gene repertoire. We have recently demonstrated that EWS-FLI-1 can alter microRNA (miRNA expression and that miRNA145 is a direct EWS-FLI-1 target whose suppression is implicated in ESFT development. Here, we use miRNA arrays to compare the global miRNA expression profile of human mesenchymal stem cells (MSC and ESFT cell lines, and show that ESFT display a distinct miRNA signature that includes induction of the oncogenic miRNA 17-92 cluster and repression of the tumor suppressor let-7 family. We demonstrate that direct repression of let-7a by EWS-FLI-1 participates in the tumorigenic potential of ESFT cells in vivo. The mechanism whereby let-7a expression regulates ESFT growth is shown to be mediated by its target gene HMGA2, as let-7a overexpression and HMGA2 repression both block ESFT cell tumorigenicity. Consistent with these observations, systemic delivery of synthetic let-7a into ESFT-bearing mice restored its expression in tumor cells, decreased HMGA2 expression levels and resulted in ESFT growth inhibition in vivo. Our observations provide evidence that deregulation of let-7a target gene expression participates in ESFT development and identify let-7a as promising new therapeutic target for one of the most aggressive pediatric malignancies.

13 CFR 124.703 - Who is eligible to receive 7(j) assistance?

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2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Who is eligible to receive 7(j) assistance? 124.703 Section 124.703 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION 8(a) BUSINESS DEVELOPMENT/SMALL DISADVANTAGED BUSINESS STATUS DETERMINATIONS 8(a) Business Development...

7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity.

Science.gov (United States)

Wypijewska, Anna; Bojarska, Elzbieta; Lukaszewicz, Maciej; Stepinski, Janusz; Jemielity, Jacek; Davis, Richard E; Darzynkiewicz, Edward

2012-10-09

Decapping scavenger (DcpS) enzymes catalyze the cleavage of a residual cap structure following 3' → 5' mRNA decay. Some previous studies suggested that both m(7)GpppG and m(7)GDP were substrates for DcpS hydrolysis. Herein, we show that mononucleoside diphosphates, m(7)GDP (7-methylguanosine diphosphate) and m(3)(2,2,7)GDP (2,2,7-trimethylguanosine diphosphate), resulting from mRNA decapping by the Dcp1/2 complex in the 5' → 3' mRNA decay, are not degraded by recombinant DcpS proteins (human, nematode, and yeast). Furthermore, whereas mononucleoside diphosphates (m(7)GDP and m(3)(2,2,7)GDP) are not hydrolyzed by DcpS, mononucleoside triphosphates (m(7)GTP and m(3)(2,2,7)GTP) are, demonstrating the importance of a triphosphate chain for DcpS hydrolytic activity. m(7)GTP and m(3)(2,2,7)GTP are cleaved at a slower rate than their corresponding dinucleotides (m(7)GpppG and m(3)(2,2,7)GpppG, respectively), indicating an involvement of the second nucleoside for efficient DcpS-mediated digestion. Although DcpS enzymes cannot hydrolyze m(7)GDP, they have a high binding affinity for m(7)GDP and m(7)GDP potently inhibits DcpS hydrolysis of m(7)GpppG, suggesting that m(7)GDP may function as an efficient DcpS inhibitor. Our data have important implications for the regulatory role of m(7)GDP in mRNA metabolic pathways due to its possible interactions with different cap-binding proteins, such as DcpS or eIF4E.

Neopterin/7,8-dihydroneopterin is elevated in Duchenne muscular dystrophy patients and protects mdx skeletal muscle function.

Science.gov (United States)

Lindsay, Angus; Schmiechen, Alexandra; Chamberlain, Christopher M; Ervasti, James M; Lowe, Dawn A

2018-05-23

Macrophage infiltration is a hallmark of dystrophin-deficient muscle. We tested the hypothesis that Duchenne muscular dystrophy (DMD) patients would have elevated levels of the macrophage synthesized pterins, neopterin and 7,8-dihydroneopterin compared to unaffected age-matched controls. Urinary neopterin/creatinine and 7,8-dihydroneopterin/creatinine were elevated in DMD patients and 7,8-dihydroneopterin/creatinine was associated with patient age and ambulation. 7,8-dihydroneopterin correction with specific gravity was also elevated in DMD patients. Because 7,8-dihydroneopterin is an antioxidant, we then identified a potential role for 7,8-dihydroneopterin in disease pathology. We assessed whether 7,8-dihydroneopterin could 1) protect against isometric force loss in wildtype skeletal muscle exposed to various pro-oxidants, and 2) protect wildtype and mdx muscle from eccentric contraction-induced force drop which has an oxidative component. Force drop was elicited in isolated Extensor Digitorum Longus (EDL) muscles by 10 eccentric contractions and recovery of force following the contractions was measured in the presence of exogenous 7,8-dihydroneopterin. 7,8-dihydroneopterin attenuated isometric force loss by wildtype EDL muscles when challenged by H 2 O 2 and HOCl, but exacerbated force loss when challenged by SIN-1 (NO · , O 2 · , ONOO - ). 7,8-dihydroneopterin attenuated eccentric contraction-induced force drop in mdx muscle. Isometric force by EDL muscles of mdx mice also recovered to a greater degree following eccentric contractions in the presence of 7,8-dihydroneopterin. The results corroborate macrophage activation in DMD patients, provide a potential protective role for 7,8-dihydroneopterin in the susceptibility of dystrophic muscle to eccentric contractions and indicate oxidative stress contributes to eccentric contraction-induced force drop in mdx skeletal muscle. This article is protected by copyright. All rights reserved. This article is protected by

A homolog of Subtilisin-like Proprotein Convertase 7 is essential to anterior neural development in Xenopus.

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Sema Senturker

Full Text Available BACKGROUND: Subtilisin-like Proprotein Convertase 7 (SPC7 is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the bone morphogenetic protein (BMP family of signaling molecules. Other SPCs are known to be required during embryonic development but corresponding data regarding SPC7 have not been reported previously. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that Xenopus SPC7 (SPC7 was expressed predominantly in the developing brain and eye, throughout the neural plate initially, then more specifically in the lens and retina primordia as development progressed. Since no prior functional information has been reported for SPC7, we used gain- and loss-of-function experiments to investigate the possibility that it may also convey patterning or tissue specification information similarly to Furin, SPC4, and SPC6. Overexpression of SPC7 was without effect. In contrast, injection of SPC7 antisense morpholino oligonucleotides (MO into a single blastomere at the 2- or 4-cell stage produced marked disruption of head structures; anophthalmia was salient. Bilateral injections suppressed head and eye formation completely. In parallel with suppression of eye and brain development by SPC7 knockdown, expression of early anterior neural markers (Sox2, Otx2, Rx2, and Pax6 and late eye-specific markers (β-Crystallin and Opsin, and of BMP target genes such as Tbx2 and Tbx3, was reduced or eliminated. Taken together, these findings suggest a critical role for SPC7-perhaps, at least in part, due to activation of one or more BMPs-in early patterning of the anterior neural plate and its derivatives. CONCLUSION/SIGNIFICANCE: SPC7 is required for normal development of the eye and brain, possibly through processing BMPs, though other potential substrates cannot be excluded.

A Homolog of Subtilisin-Like Proprotein Convertase 7 Is Essential to Anterior Neural Development in Xenopus

Science.gov (United States)

Senturker, Sema; Thomas, John Terrig; Mateshaytis, Jennifer; Moos, Malcolm

2012-01-01

Background Subtilisin-like Proprotein Convertase 7 (SPC7) is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the bone morphogenetic protein (BMP) family of signaling molecules. Other SPCs are known to be required during embryonic development but corresponding data regarding SPC7 have not been reported previously. Methodology/Principal Findings We demonstrated that Xenopus SPC7 (SPC7) was expressed predominantly in the developing brain and eye, throughout the neural plate initially, then more specifically in the lens and retina primordia as development progressed. Since no prior functional information has been reported for SPC7, we used gain- and loss-of-function experiments to investigate the possibility that it may also convey patterning or tissue specification information similarly to Furin, SPC4, and SPC6. Overexpression of SPC7 was without effect. In contrast, injection of SPC7 antisense morpholino oligonucleotides (MO) into a single blastomere at the 2- or 4-cell stage produced marked disruption of head structures; anophthalmia was salient. Bilateral injections suppressed head and eye formation completely. In parallel with suppression of eye and brain development by SPC7 knockdown, expression of early anterior neural markers (Sox2, Otx2, Rx2, and Pax6) and late eye-specific markers (β-Crystallin and Opsin), and of BMP target genes such as Tbx2 and Tbx3, was reduced or eliminated. Taken together, these findings suggest a critical role for SPC7–perhaps, at least in part, due to activation of one or more BMPs–in early patterning of the anterior neural plate and its derivatives. Conclusion/Significance SPC7 is required for normal development of the eye and brain, possibly through processing BMPs, though other potential substrates cannot be excluded. PMID:22761776

Number of active transcription factor binding sites is essential for the Hes7 oscillator

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de Angelis Martin

2006-02-01

Full Text Available Abstract Background It is commonly accepted that embryonic segmentation of vertebrates is regulated by a segmentation clock, which is induced by the cycling genes Hes1 and Hes7. Their products form dimers that bind to the regulatory regions and thereby repress the transcription of their own encoding genes. An increase of the half-life of Hes7 protein causes irregular somite formation. This was shown in recent experiments by Hirata et al. In the same work, numerical simulations from a delay differential equations model, originally invented by Lewis, gave additional support. For a longer half-life of the Hes7 protein, these simulations exhibited strongly damped oscillations with, after few periods, severely attenuated the amplitudes. In these simulations, the Hill coefficient, a crucial model parameter, was set to 2 indicating that Hes7 has only one binding site in its promoter. On the other hand, Bessho et al. established three regulatory elements in the promoter region. Results We show that – with the same half life – the delay system is highly sensitive to changes in the Hill coefficient. A small increase changes the qualitative behaviour of the solutions drastically. There is sustained oscillation and hence the model can no longer explain the disruption of the segmentation clock. On the other hand, the Hill coefficient is correlated with the number of active binding sites, and with the way in which dimers bind to them. In this paper, we adopt response functions in order to estimate Hill coefficients for a variable number of active binding sites. It turns out that three active transcription factor binding sites increase the Hill coefficient by at least 20% as compared to one single active site. Conclusion Our findings lead to the following crucial dichotomy: either Hirata's model is correct for the Hes7 oscillator, in which case at most two binding sites are active in its promoter region; or at least three binding sites are active, in which

Interleukin-7 Availability Is Maintained by a Hematopoietic Cytokine Sink Comprising Innate Lymphoid Cells and T Cells.

Science.gov (United States)

Martin, Christopher E; Spasova, Darina S; Frimpong-Boateng, Kwesi; Kim, Hee-Ok; Lee, Minji; Kim, Kwang Soon; Surh, Charles D

2017-07-18

Interleukin-7 (IL-7) availability determines the size and proliferative state of the resting T cell pool. However, the mechanisms that regulate steady-state IL-7 amounts are unclear. Using experimental lymphopenic mouse models and IL-7-induced homeostatic proliferation to measure IL-7 availability in vivo, we found that radioresistant cells were the source of IL-7 for both CD4 + and CD8 + T cells. Hematopoietic lineage cells, although irrelevant as a source of IL-7, were primarily responsible for limiting IL-7 availability via their expression of IL-7R. Unexpectedly, innate lymphoid cells were found to have a potent influence on IL-7 amounts in the primary and secondary lymphoid tissues. These results demonstrate that IL-7 homeostasis is achieved through consumption by multiple subsets of innate and adaptive immune cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Nuclear thioredoxin-1 is required to suppress cisplatin-mediated apoptosis of MCF-7 cells

International Nuclear Information System (INIS)

Chen, Xiao-Ping; Liu, Shou; Tang, Wen-Xin; Chen, Zheng-Wang

2007-01-01

Different cell line with increased thioredoxin-1 (Trx-1) showed a decreased or increased sensitivity to cell killing by cisplatin. Recently, several studies found that the subcellular localization of Trx-1 is closely associated with its functions. In this study, we explored the association of the nuclear Trx-1 with the cisplatin-mediated apoptosis of breast cancer cells MCF-7. Firstly, we found that higher total Trx-1 accompanied by no change of nuclear Trx-1 can not influence apoptosis induced by cisplatin in MCF-7 cells transferred with Trx-1 cDNA. Secondly, higher nuclear Trx-1 accompanied by no change of total Trx-1 can protect cells from apoptosis induced by cisplatin. Thirdly, high nuclear Trx-1 involves in the cisplatin-resistance in cisplatin-resistive cells. Meanwhile, we found that the mRNA level of p53 is closely correlated with the level of nuclear Trx-1. In summary, we concluded that the nuclear Trx-1 is required to resist apoptosis of MCF-7 cells induced by cisplatin, probably through up-regulating the anti-apoptotic gene, p53

The level of claudin-7 is reduced as an early event in colorectal carcinogenesis

DEFF Research Database (Denmark)

Lange, Jette Bornholdt; Friis, Stine; Godiksen, Sine

2011-01-01

-regulation of the oncogenic serine protease, matriptase, induces leakiness in epithelial barriers both in vivo and in vitro. We found in an in-silico search tight co-regulation between matriptase and claudin-7 expression. We have previously shown that the matriptase expression level decreases during colorectal carcinogenesis....... In the present study we investigated whether claudin-7 expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue....

Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock

OpenAIRE

Bessho, Yasumasa; Hirata, Hiromi; Masamizu, Yoshito; Kageyama, Ryoichiro

2003-01-01

Hes7, a bHLH gene essential for somitogenesis, displays cyclic expression of mRNA in the presomitic mesoderm (PSM). Here, we show that Hes7 protein is also expressed in a dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed that Hes7 and Lunatic fringe (Lfng) transcription occurs in the Hes7 protein-negative domains. Furthermore, Hes7 and Lfng transcription is constitutively up-regulated in the absence of Hes7 protein and down-regulated by stabi...

7 CFR 170.2 - Is the USDA Farmers Market a producer-only market?

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Is the USDA Farmers Market a producer-only market? 170...) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.2 Is the USDA Farmers Market a producer-only market? Yes. A producer-only market is one that does not offer...

Pdlim7 Regulates Arf6-Dependent Actin Dynamics and Is Required for Platelet-Mediated Thrombosis in Mice.

Directory of Open Access Journals (Sweden)

Alexander E Urban

Full Text Available Upon vessel injury, platelets become activated and rapidly reorganize their actin cytoskeleton to adhere to the site of endothelial damage, triggering the formation of a fibrin-rich plug to prevent further blood loss. Inactivation of Pdlim7 provides the new perspective that regulation of actin cytoskeletal changes in platelets is dependent on the encoded PDZ-LIM protein. Loss-of-function of Pdlim7 triggers hypercoagulopathy and causes significant perinatal lethality in mice. Our in vivo and in vitro studies reveal that Pdlim7 is dynamically distributed along actin fibers, and lack of Pdlim7 leads to a marked inability to rearrange the actin cytoskeleton. Specifically, the absence of Pdlim7 prevents platelets from bundling actin fibers into a concentric ring that defines the round spread shape of activated platelets. Similarly, in mouse embryonic fibroblasts, loss of Pdlim7 abolishes the formation of stress fibers needed to adopt the typical elongated fibroblast shape. In addition to revealing a fundamental cell biological role in actin cytoskeletal organization, we also demonstrate a function of Pdlim7 in regulating the cycling between the GTP/GDP-bound states of Arf6. The small GTPase Arf6 is an essential factor required for actin dynamics, cytoskeletal rearrangements, and platelet activation. Consistent with our findings of significantly elevated initial F-actin ratios and subsequent morphological aberrations, loss of Pdlim7 causes a shift in balance towards an increased Arf6-GTP level in resting platelets. These findings identify a new Pdlim7-Arf6 axis controlling actin dynamics and implicate Pdlim7 as a primary endogenous regulator of platelet-dependent hemostasis.

PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome

Science.gov (United States)

Ebermann, Inga; Phillips, Jennifer B.; Liebau, Max C.; Koenekoop, Robert K.; Schermer, Bernhard; Lopez, Irma; Schäfer, Ellen; Roux, Anne-Francoise; Dafinger, Claudia; Bernd, Antje; Zrenner, Eberhart; Claustres, Mireille; Blanco, Bernardo; Nürnberg, Gudrun; Nürnberg, Peter; Ruland, Rebecca; Westerfield, Monte; Benzing, Thomas; Bolz, Hanno J.

2010-01-01

Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease. PMID:20440071

PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome.

Science.gov (United States)

Ebermann, Inga; Phillips, Jennifer B; Liebau, Max C; Koenekoop, Robert K; Schermer, Bernhard; Lopez, Irma; Schäfer, Ellen; Roux, Anne-Francoise; Dafinger, Claudia; Bernd, Antje; Zrenner, Eberhart; Claustres, Mireille; Blanco, Bernardo; Nürnberg, Gudrun; Nürnberg, Peter; Ruland, Rebecca; Westerfield, Monte; Benzing, Thomas; Bolz, Hanno J

2010-06-01

Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain-containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein-coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease.

ATP7A is a novel target of retinoic acid receptor β2 in neuroblastoma cells

Science.gov (United States)

Bohlken, A; Cheung, B B; Bell, J L; Koach, J; Smith, S; Sekyere, E; Thomas, W; Norris, M; Haber, M; Lovejoy, D B; Richardson, D R; Marshall, G M

2009-01-01

Increased retinoic acid receptor β (RARβ2) gene expression is a hallmark of cancer cell responsiveness to retinoid anticancer effects. Moreover, low basal or induced RARβ2 expression is a common feature of many human cancers, suggesting that RARβ2 may act as a tumour suppressor gene in the absence of supplemented retinoid. We have previously shown that low RARβ2 expression is a feature of advanced neuroblastoma. Here, we demonstrate that the ABC domain of the RARβ2 protein alone was sufficient for the growth inhibitory effects of RARβ2 on neuroblastoma cells. ATP7A, the copper efflux pump, is a retinoid-responsive gene, was upregulated by ectopic overexpression of RARβ2. The ectopic overexpression of the RARβ2 ABC domain was sufficient to induce ATP7A expression, whereas, RARβ2 siRNA blocked the induction of ATP7A expression in retinoid-treated neuroblastoma cells. Forced downregulation of ATP7A reduced copper efflux and increased viability of retinoid-treated neuroblastoma cells. Copper supplementation enhanced cell growth and reduced retinoid-responsiveness, whereas copper chelation reduced the viability and proliferative capacity. Taken together, our data demonstrates ATP7A expression is regulated by retinoic acid receptor β and it has effects on intracellular copper levels, revealing a link between the anticancer action of retinoids and copper metabolism. PMID:19127267

PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells.

Directory of Open Access Journals (Sweden)

Michael D Brooks

Full Text Available Cell-cell interactions between tumor cells and constituents of their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM cells and endothelial cells (ECs establish a purported cancer stem cell niche. We hypothesized that genes regulated by these interactions would be important, particularly as therapeutic targets. Using a computational approach, we deconvoluted expression data from a mixed physical co-culture of GBM cells and ECs and identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to direct contact with ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation in vitro and increased tumor growth and aggressiveness in an in vivo intracranial GBM model. Collectively these studies illustrate a novel approach for studying cell-cell interactions and identifying new therapeutic targets like PDE7B in GBM.

Water pollution and distribution of the black fly (Diptera: Simuliidae) in the Atlantic Forest, Brazil.

Science.gov (United States)

Docile, Tatiana N; Figueiró, Ronaldo; Gil-Azevedo, Leonardo H; Nessimian, Jorge L

2015-09-01

Black flies have medical importance because some species are vectors of the unenocerciasis and Mansonelosis, nevertheless, their ecology and potential use as bioindicators is still poorly studied in the Neotropical Region. In Brazil, bioindicators use is strongly focused in a multimetrical ecological index approach; this way, we investigated the black fly spatial distribution, in relation to abiotic factors correlated to water quality, to provide baseline information for their utilization as standalone indicators of lotic systems integrity. We have tested the hypothesis that environmental changes related to urbanization, lead to decreased abundance and loss in the number of species of the black fly fauna. The sampling was conducted in 10 urban and 10 preserved streams during the dry season (August-September) of 2012, in the mountainous region of Teres6polis, State of Rio de Janeiro, Brazil. The streams were characterized for their environmental integrity conditions and physico-chemical properties of water. In each stream, five different rapid points were sampled in a section of 50 meters, 10 meters apart from each other. The black flies were sampled with a kick-net sampler on rocky substrates. The material was separated and the larvae were sorted in morphotypes, and later, the final instar specimens were dissected and identified with the help of taxonomical literature at species level. A total abundance of 488 larvae from nine species were collected, 5 (1.02 %) in extremely impacted streams, 470 (96.31 %) in intermediate streams and 13 (2.66 %) in preserved streams. The visual evaluation (HII) differed in relation to the water physico-chemical evaluation, in which more variation in the characterization of the sampling sites was observed. In Canonical Correspondence Analysis Simulium subpallidum, S. inscrustatum and S. pertinax were significantly associated with intermediate values of most of the variables, and then to intermediate impacted sites. On the other hand

TRPM7 is required within zebrafish sensory neurons for the activation of touch-evoked escape behaviors

Science.gov (United States)

Low, Sean E.; Amburgey, Kimberly; Horstick, Eric; Linsley, Jeremy; Sprague, Shawn M.; Cui, Wilson W.; Zhou, Weibin; Hirata, Hiromi; Saint-Amant, Louis; Hume, Richard I.; Kuwada, John Y.

2011-01-01

Mutations in the gene encoding TRPM7 (trpm7), a member of the TRP superfamily of cation channels that possesses an enzymatically active kinase at its carboxyl terminus, cause the touch-unresponsive zebrafish mutant touchdown. We identified and characterized a new allele of touchdown, as well as two previously reported alleles, and found that all three alleles harbor mutations which abolish channel activity. Through the selective restoration of TRPM7 expression in sensory neurons we found that TRPM7’s kinase activity, and selectivity for divalent cations over monovalent cations, were dispensable for touch-evoked activation of escape behaviors in zebrafish. Additional characterization revealed that sensory neurons were present and capable of responding to tactile stimuli in touchdown mutants, indicating that TRPM7 is not required for sensory neuron survival or mechanosensation. Finally, exposure to elevated concentrations of divalent cations was found to restore touch-evoked behaviors in touchdown mutants. Collectively these findings are consistent with a role for zebrafish TRPM7 within sensory neurons in the modulation of neurotransmitter release at central synapses, similar to that proposed for mammalian TRPM7 at peripheral synapses. PMID:21832193

Arabidopsis ACA7, encoding a putative auto-regulated Ca(2+)-ATPase, is required for normal pollen development.

Science.gov (United States)

Lucca, Noel; León, Gabriel

2012-04-01

Microgametogenesis is a complex process that involves numerous well-coordinated cell activities, ending with the production of pollen grains. Pollen development has been studied at the cytological level in Arabidopsis and other plant species, where its temporal time course has been defined. However, the molecular mechanism underlying this process is still unclear, since a relative small number of genes and/or processes have been identified as essential for pollen development. We have designed a methodology to select candidate genes for functional analysis, based on transcriptomic data obtained from different stages of pollen development. From our analyses, we selected At2g22950 as a candidate gene; this gene encodes a protein belonging to the auto-regulated Ca(2+)-ATPase family, ACA7. Microarray data indicate that ACA7 is expressed exclusively in developing pollen grains, with the highest level of mRNA at the time of the second pollen mitosis. Our RT-PCR experiments showed that ACA7 mRNA is detected exclusively in developing flowers. Confocal microscopy experiments showed a plasma membrane localization for the recombinant GFP:ACA7 protein. We identified two different insertional mutant lines, aca7-1 and aca7-2; plants from both mutant lines displayed a normal vegetative development but showed large amounts of dead pollen grains in mature flowers assayed by Alexander's staining. Histological analysis indicated that abnormalities are detected after the first pollen mitosis and we found a strong correlation between ACA7 mRNA accumulation and the severity of the phenotype. Our results indicate that ACA7 is a plasma membrane protein that has an important role during pollen development, possibly through regulation of Ca(2+) homeostasis. © Springer-Verlag 2011

Samd7 is a cell type-specific PRC1 component essential for establishing retinal rod photoreceptor identity.

Science.gov (United States)

Omori, Yoshihiro; Kubo, Shun; Kon, Tetsuo; Furuhashi, Mayu; Narita, Hirotaka; Kominami, Taro; Ueno, Akiko; Tsutsumi, Ryotaro; Chaya, Taro; Yamamoto, Haruka; Suetake, Isao; Ueno, Shinji; Koseki, Haruhiko; Nakagawa, Atsushi; Furukawa, Takahisa

2017-09-26

Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7- null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7 -deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity.

distribution of simulium species and its infection with onchocerca

African Journals Online (AJOL)

DR. AMINU

. Detection of the parasites in the vector was attained by dissection of flies under dissecting microscope. The result revealed that the prevalence of microfilariae among insects collected in the months July and August was 23.08% and 21.47%.

Tetratricopeptide repeat protein Pyg7 is essential for photosystem I assembly by interacting with PsaC in Arabidopsis.

Science.gov (United States)

Yang, Huixia; Li, Pin; Zhang, Aihong; Wen, Xiaogang; Zhang, Lixin; Lu, Congming

2017-09-01

Although progress has been made in determining the structure and understanding the function of photosystem I (PSI), the PSI assembly process remains poorly understood. PsaC is an essential subunit of PSI and participates in the transfer of electrons to ferredoxin. However, how PsaC is assembled during accumulation of the PSI complex is unknown. In the present study, we showed that Pyg7 localized to the stromal thylakoid and associated with the PSI complex. We also showed that Pyg7 interacted with PsaC. Furthermore, we found that the PSI assembly process was blocked following formation of the PsaAB heterodimer in the pyg7 mutant. In addition, the analyses of PSI stability in Pyg7RNAi plants showed that Pyg7 is involved in maintaining the assembled PSI complex under excess-light conditions. Moreover, we demonstrated that decreased Pyg7 content resulted in decreased efficiency of PSI assembly in Pyg7RNAi plants. These findings suggest that the role of Pyg7 in PSI biogenesis has evolved as an essential assembly factor by interacting with PsaC in Arabidopsis, in addition to being a stability factor for PSI as seen in Synechocystis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

The TIR-domain containing adaptor TRAM is required for TLR7 mediated RANTES production.

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Enda Shevlin

Full Text Available Toll-like receptor 7 (TLR7 plays a vital role in the immune response to ssRNA viruses such as human rhinovirus (HRV and Influenza, against which there are currently no treatments or vaccines with long term efficacy available. Clearly, a more comprehensive understanding of the TLR7 signaling axis will contribute to its molecular targeting. TRIF related adaptor molecule (TRAM plays a vital role in TLR4 signaling by recruiting TRIF to TLR4, followed by endosomal trafficking of the complex and initiation of IRF3 dependent type I interferon production as well as NF-κB dependent pro-inflammatory cytokine production. Towards understanding the molecular mechanisms that regulate TLR7 functionality, we found that TRAM(-/- murine macrophages exhibited a transcriptional and translational impairment in TLR7 mediated RANTES, but not TNFα, production. Suppression of TRAM expression in human macrophages also resulted in an impairment in TLR7 mediated CCL5 and IFN-β, but not TNFα, gene induction. Furthermore, suppression of endogenous human TRAM expression in human macrophages significantly impaired RV16 induced CCL5 and IFNβ, but not TNFα gene induction. Additionally, TRAM-G2A dose-dependently inhibited TLR7 mediated activation of CCL5, IFNβ and IFNα reporter genes. TLR7-mediated phosphorylation and nuclear translocation of IRF3 was impaired in TRAM(-/- cells. Finally, co-immunoprecipitation studies indicated that TRAM physically interacts with MyD88 upon TLR7 stimulation, but not under basal conditions. Our results clearly demonstrate that TRAM plays a, hitherto unappreciated, role in TLR7 signaling through a novel signaling axis containing, but not limited to, MyD88, TRAM and IRF3 towards the activation of anti-viral immunity.

Pri-let-7a-1 rs10739971 polymorphism is associated with gastric cancer prognosis and might affect mature let-7a expression

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Li Y

2016-07-01

Full Text Available Ying Li, Qian Xu, Jingwei Liu, Caiyun He, Quan Yuan, Chengzhong Xing, Yuan Yuan Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University, Liaoning Provincial Education Department, Shenyang, People’s Republic of China Abstract: The relationship between the pri-let-7a-1 rs10739971 polymorphism and gastric cancer (GC risk has been reported. However, the role of this polymorphism in the prognosis of GC remains largely elusive. Sequenom MassARRAY platform method and the polymerase chain reaction (PCR-restriction fragment length polymorphism were used to investigate pri-let-7a-1 rs10739971 G→A in 334 GC patients. Real-time PCR detected expression of mature let-7a in serum and tissue. Patients with AA or GA+AA genotypes of the pri-let-7a-1 rs10739971 polymorphism demonstrated significantly longer survival time than those with the wild GG genotype. Stratified analysis indicated that survival time was significantly longer in women with AA or GA+AA genotypes and in Borrmann type I/II patients with GA heterozygote or GA+AA genotypes. AA genotype was more frequent in the lymphatic-metastasis-negative subgroup. Serum mature let-7a expression in healthy people with the GA heterozygote and the GA+AA genotype was higher than in those with the GG genotype, and the difference remained significant in the female healthy subgroup. Pri-let-7a-1 rs10739971 polymorphism might be a biomarker for GC prognosis, especially for female and Borrmann type I/II patients. The pri-let-7a-1 rs10739971 polymorphism might affect serum mature let-7a expression, and partly explain the mechanism of the relationship between the pri-let-7a-1 rs10739971 polymorphism and GC survival. Keywords: miRNA, let-7a, polymorphism, gastric cancer, prognosis, expression

The emerin-binding transcription factor Lmo7 is regulated by association with p130Cas at focal adhesions

Directory of Open Access Journals (Sweden)

Michele A. Wozniak

2013-08-01

Full Text Available Loss of function mutations in the nuclear inner membrane protein, emerin, cause X-linked Emery-Dreifuss muscular dystrophy (X-EDMD. X-EDMD is characterized by contractures of major tendons, skeletal muscle weakening and wasting, and cardiac conduction system defects. The transcription factor Lmo7 regulates muscle- and heart-relevant genes and is inhibited by binding to emerin, suggesting Lmo7 misregulation contributes to EDMD disease. Lmo7 associates with cell adhesions and shuttles between the plasma membrane and nucleus, but the regulation and biological consequences of this dual localization were unknown. We report endogenous Lmo7 also associates with focal adhesions in cells, and both co-localizes and co-immunoprecipitates with p130Cas, a key signaling component of focal adhesions. Lmo7 nuclear localization and transcriptional activity increased significantly in p130Cas-null MEFs, suggesting Lmo7 is negatively regulated by p130Cas-dependent association with focal adhesions. These results support EDMD models in which Lmo7 is a downstream mediator of integrin-dependent signaling that allows tendon cells and muscles to adapt to and withstand mechanical stress.

Hepatocellular differentiation status is characterized by distinct subnuclear localization and form of the chanzyme TRPM7.

Science.gov (United States)

Ogunrinde, Adenike; Pereira, Robyn D; Beaton, Natalie; Lam, D Hung; Whetstone, Christiane; Hill, Ceredwyn E

The channel-kinase TRPM7 is important for the survival, proliferation, and differentiation, of many cell types. Both plasma membrane channel activity and kinase function are implicated in these roles. Channel activity is greater in less differentiated hepatoma cells compared with non-dividing, terminally differentiated adult hepatocytes, suggesting differences in protein expression and/or localization. We used electrophysiological and immunofluorescence approaches to establish whether hepatocellular differentiation is associated with altered TRPM7 expression. Mean outward current decreased by 44% in WIF-B hepatoma cells incubated with the established hepatic differentiating factors oncostatin M/dexamethasone for 1-8 days. Pre-incubation with pyridone 6, a pan-JAK inhibitor, blocked the current reduction. An antibody targeted to the C-terminus of TRPM7 labelled the cytoplasm in WIF-B cells and intact rat liver. Significant label also localized to the nuclear envelope (NE), with relatively more detected in adult hepatocytes compared with WIF-B cells. Hepatoma cells also exhibited nucleoplasmic labelling with intense signal in the nucleolus. The endogenous labelling pattern closely resembles that of HEK293T cells heterologously expressing a TRPM7 kinase construct containing a putative nucleolar localization sequence. These results suggest that TRPM7 form and distribution between the plasma membrane and nucleus, rather than expression, is altered in parallel with differentiation status in rat hepatic cells. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer

International Nuclear Information System (INIS)

Loos, Martin; Hedderich, Dennis M; Ottenhausen, Malte; Giese, Nathalia A; Laschinger, Melanie; Esposito, Irene; Kleeff, Jörg; Friess, Helmut

2009-01-01

Costimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer. B7-H3 expression was evaluated by immunohistochemistry in 68 patients with pancreatic cancer who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells. B7-H3 expression was significantly upregulated in pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with high tumor B7-H3 levels had a significantly better postoperative prognosis than patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3 expression significantly correlated with the number of tumor-infiltrating CD8+ T cells (p = 0.018). We demonstrate for the first time that B7-H3 is abundantly expressed in pancreatic cancer and that tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival. Our findings suggest that B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer

Let-7i-Induced Atg4B Suppression Is Essential for Autophagy of Placental Trophoblast in Preeclampsia.

Science.gov (United States)

Xu, Yinyan; Huang, Xinyan; Xie, Juan; Chen, Yanni; Fu, Jing; Wang, Li

2017-09-01

Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

USP7 Is a Suppressor of PCNA Ubiquitination and Oxidative-Stress-Induced Mutagenesis in Human Cells.

Science.gov (United States)

Kashiwaba, Shu-ichiro; Kanao, Rie; Masuda, Yuji; Kusumoto-Matsuo, Rika; Hanaoka, Fumio; Masutani, Chikahide

2015-12-15

Mono-ubiquitinated PCNA activates error-prone DNA polymerases; therefore, strict regulation of PCNA mono-ubiquitination is crucial in avoiding undesired mutagenesis. In this study, we used an in vitro assay system to identify USP7 as a deubiquitinating enzyme of mono-ubiquitinated PCNA. Suppression of USP1, a previously identified PCNA deubiquitinase, or USP7 increased UV- and H2O2-induced PCNA mono-ubiquitination in a distinct and additive manner, suggesting that USP1 and USP7 make different contributions to PCNA deubiquitination in human cells. Cell-cycle-synchronization analyses revealed that USP7 suppression increased H2O2-induced PCNA ubiquitination throughout interphase, whereas USP1 suppression specifically increased ubiquitination in S-phase cells. UV-induced mutagenesis was elevated in USP1-suppressed cells, whereas H2O2-induced mutagenesis was elevated in USP7-suppressed cells. These results suggest that USP1 suppresses UV-induced mutations produced in a manner involving DNA replication, whereas USP7 suppresses H2O2-induced mutagenesis involving cell-cycle-independent processes such as DNA repair. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Is the $7/2_1^-$ Isomer State of $^{43}$S Spherical?

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Chevrier, R; Gaudefroy, L; Ichikawa, Y; Ueno, H; Hass, M; Haas, H; Cottenier, S; Aoi, N; Asahi, K; Balabanski, D L; Fukuda, N; Furukawa, T; Georgiev, G; Hayashi, H; Iijima, H; Inabe, N; Inoue, T; Ishihara, M; Ishii, Y; Kameda, D; Kubo, T; Nanao, T; Neyens, G; Ohnishi, T; Rajabali, M M; Suzuki, K; Takeda, H; Tsuchiya, M; Vermeulen, N; Watanabe, H; Yoshimi, A

2012-01-01

We report on the spectroscopic quadrupole moment measurement of the 7/2−1 isomeric state in S271643 [E∗=320.5(5)  keV, T1/2=415(3)  ns], using the time dependent perturbed angular distribution technique at the RIKEN RIBF facility. Our value, ∣Qs∣=23(3)  efm2, is larger than that expected for a single-particle state. Shell model calculations using the modern SDPF-U interaction for this mass region reproduce remarkably well the measured ∣Qs∣, and show that non-negligible correlations drive the isomeric state away from a purely spherical shape.

Importin-α7 Is Involved in the Formation of Ebola Virus Inclusion Bodies but Is Not Essential for Pathogenicity in Mice.

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Gabriel, Gülsah; Feldmann, Friederike; Reimer, Rudolph; Thiele, Swantje; Fischer, Meike; Hartmann, Enno; Bader, Michael; Ebihara, Hideki; Hoenen, Thomas; Feldmann, Heinz

2015-10-01

Ebola virus (EBOV) protein 24 antagonizes the host interferon (IFN) response by hijacking select nuclear importin-α isoforms. Thereby, it blocks STAT1-mediated IFN-α/β and IFN-γ synthesis. However, owing to the lack of importin-α knockout animal models in the past, their role in EBOV pathogenesis remained largely unknown. Here, we demonstrate that importin-α7 is involved in the formation of EBOV inclusion bodies and replication. However, deletion of the gene encoding importin-α7 was not sufficient to increase survival rates among mice infected with EBOV. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

SIRT1 activation with neuroheal is neuroprotective but SIRT2 inhibition with AK7 is detrimental for disconnected motoneurons.

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Romeo-Guitart, David; Leiva-Rodríguez, Tatiana; Espinosa-Alcantud, María; Sima, Núria; Vaquero, Alejandro; Domínguez-Martín, Helena; Ruano, Diego; Casas, Caty

2018-05-10

Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy. This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non-apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IRE1α and XBP1 by 21 days post injury. Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron-like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model. In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged MN survival. To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells. In this system, AK7 treatment of ER-stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-κB and the consequent transcription of cytotoxic pro-inflammatory factors similarly. The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment.

13 CFR 124.701 - What is the purpose of the 7(j) management and technical assistance program?

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2010-01-01

...) Business Development Management and Technical Assistance Program § 124.701 What is the purpose of the 7(j... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What is the purpose of the 7(j) management and technical assistance program? 124.701 Section 124.701 Business Credit and Assistance SMALL...

CD95 is part of a let-7/p53/miR-34 regulatory network.

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Annika Hau

Full Text Available The death receptor CD95 (APO-1/Fas mediates apoptosis induction upon ligation by its cognate ligand CD95L. Two types of CD95 signaling pathways have been identified, which are characterized by the absence (Type I or presence (Type II of mitochondrial involvement. Micro(miRNAs are small noncoding RNAs that negatively regulate gene expression. They are important regulators of differentiation processes and are found frequently deregulated in many human cancers. We recently showed that Type I cells express less of the differentiation marker miRNA let-7 and, hence, likely represent more advanced tumor cells than the let-7 high expressing Type II cells. We have now identified miR-34a as a selective marker for cells that are sensitive to CD95-mediated apoptosis. Both CD95 and miR-34a are p53 target genes, and consequently, both the sensitivity of cancer cells to CD95-mediated apoptosis and the ability to respond to p53 mediated DNA genotoxic stress are linked. Interestingly, while miR-34a was found to positively correlate with the ability of cells to respond to genotoxic stress, let-7 was negatively correlated. The expression level of CD95 inversely correlated with the expression of let-7 suggesting regulation of let-7 expression by CD95. To test a link between p53 and miR-34a, we altered the expression of CD95. This affected the ability of cells to activate p53 and to regulate miR-34a. Our data point to a novel regulatory network comprising p53, CD95, let-7, and miR-34a that affects cancer cell survival, differentiation, and sensitivity to apoptotic signals. The possible relevance of this regulatory network for cancer stem cells is discussed.

7 CFR 2812.7 - Costs.

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2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Costs. 2812.7 Section 2812.7 Agriculture Regulations...) § 2812.7 Costs. Donated excess personal property/equipment is free of charge. However, the donee must pay all costs associated with packaging and transportation, unless the sponsoring agency has made other...

Protein P7 of the cystovirus φ6 is located at the three-fold axis of the unexpanded procapsid.

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Garrett Katz

Full Text Available The objective of this study was to determine the location of protein P7, the RNA packaging factor, in the procapsid of the φ6 cystovirus. A comparison of cryo-electron microscopy high-resolution single particle reconstructions of the φ6 complete unexpanded procapsid, the protein P2-minus procapsid (P2 is the RNA directed RNA-polymerase, and the P7-minus procapsid, show that prior to RNA packaging the P7 protein is located near the three-fold axis of symmetry. Difference maps highlight the precise position of P7 and demonstrate that in P7-minus particles the P2 proteins are less localized with reduced densities at the three-fold axes. We propose that P7 performs the mechanical function of stabilizing P2 on the inner protein P1 shell which ensures that entering viral single-stranded RNA is replicated.

Variation in WNT7A is unlikely to be a cause of familial Congenital Talipes Equinovarus

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Hennekam Raoul

2008-06-01

Full Text Available Abstract Background Genetic factors make an important contribution to the aetiology of congenital talipes equinovarus (CTEV, the most common developmental disorder of the lower limb. WNT7A was suggested as a candidate gene for CTEV on the basis of a genome-wide scan for linkage in a large multi-case family. WNT7A is a plausible candidate gene for CTEV as it provides a signal for pattern formation during limb development, and mutation in WNT7A has been reported in a number of limb malformation syndromes. Methods We investigated the role of WNT7A using a family-based linkage approach in our large series of European multi-case CTEV families. Three microsatellite markers were used, of which one (D3S2385 is intragenic, and the other two (D3S2403, D3S1252 are 700 kb 5' to the start and 20 kb from the 3' end of the gene, respectively. Ninety-one CTEV families, comprising 476 individuals of whom 211 were affected, were genotyped. LOD scores using recessive and incomplete-dominant inheritance models, and non-parametric linkage scores, excluded linkage. Results No significant evidence for linkage was observed using either parametric or non-parametric models. LOD scores for the parametric models remained strongly negative in the regions between the markers, and in the 0.5 cM intervals outside the marker map. No significant lod scores were obtained when the data were analysed allowing for heterogeneity. Conclusion Our evidence suggests that the WNT7A gene is unlikely to be a major contributor to the aetiology of familial CTEV.

Frizzled 7 expression is positively regulated by SIRT1 and β-catenin in breast cancer cells.

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Glenn E Simmons

Full Text Available The Wnt signaling pathway is often chronically activated in diverse human tumors, and the Frizzled (FZD family of receptors for Wnt ligands, are central to propagating oncogenic signals in a β-catenin-dependent and independent manner. SIRT1 is a class III histone deacetylase (HDAC that deacetylates histone and non-histone proteins to regulate gene transcription and protein function. We previously demonstrated that SIRT1 loss of function led to a significant decrease in the levels of Dishevelled (Dvl proteins. To further explore this connection between the sirtuins and components of the Wnt pathway, we analyzed sirtuin-mediated regulation of FZD proteins. Here we explore the contribution of sirtuin deacetylases in promoting constitutive Wnt pathway activation in breast cancer cells. We demonstrate that the use of small molecule inhibitors of SIRT1 and SIRT2, and siRNA specific to SIRT1, all reduce the levels of FZD7 mRNA. We further demonstrate that pharmacologic inhibition of SIRT1/2 causes a marked reduction in FZD7 protein levels. Additionally, we show that β-catenin and c-Jun occupy the 7 kb region upstream of the transcription start site of the FZD7 gene, and SIRT1 inhibition leads to a reduction in the occupancy of both β-catenin and c-Jun at points along this region. This work uncovers a new mechanism for the regulation of FZD7 and provides a critical new link between the sirtuins and FZD7, one of the earliest nodal points from which oncogenic Wnt signaling emanates. This study shows that inhibition of specific sirtuins may provide a unique strategy for inhibiting the constitutively active Wnt pathway at the level of the receptor.

Autolytic activity of human calpain 7 is enhanced by ESCRT-III-related protein IST1 through MIT-MIM interaction.

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Osako, Yohei; Maemoto, Yuki; Tanaka, Ryohei; Suzuki, Hironori; Shibata, Hideki; Maki, Masatoshi

2010-11-01

Calpain 7, a mammalian ortholog of yeast Cpl1/Rim13 and fungal PalB, is an atypical calpain that lacks a penta-EF-hand domain. Previously, we reported that a region containing a tandem repeat of microtubule-interacting and transport (MIT) domains in calpain 7 interacts with a subset of endosomal sorting complex required for transport (ESCRT)-III-related proteins, suggesting involvement of calpain 7 in the ESCRT system. Although yeast and fungal calpains are thought to be involved in alkaline adaptation via limited proteolysis of specific transcription factors, proteolytic activity of calpain 7 has not been demonstrated yet. In this study, we investigated the interaction between calpain 7 and a newly reported ESCRT-III family member, increased sodium tolerance-1 (IST1), which possesses two different types of MIT-interacting motifs (MIM1 and MIM2). We found that glutathione-S-transferase (GST)-fused tandem MIT domains of calpain 7 (calpain 7MIT) pulled down FLAG-tagged IST1 expressed in HEK293T cells. Coimmunoprecipitation assays with various deletion or point mutants of epitope-tagged calpain 7 and IST1 revealed that both repetitive MIT domains and MIMs are required for efficient interaction. Direct MIT-MIM binding was confirmed by a pulldown experiment with GST-fused IST1 MIM and purified recombinant calpain 7MIT. Furthermore, we found that the GST-MIM protein enhances the autolysis of purified Strep-tagged monomeric green fluorescent protein (mGFP)-fused calpain 7 (mGFP-calpain 7-Strep). The autolysis was almost completely abolished by 10 mmN-ethylmaleimide but only partially inhibited by 1 mm leupeptin or E-64. The putative catalytic Cys290-substituted mutant (mGFP-calpain 7(C290S)-Strep) showed no autolytic activity. These results demonstrate for the first time that human calpain 7 is proteolytically active, and imply that calpain 7 is activated in the ESCRT system. © 2010 The Authors Journal compilation © 2010 FEBS.

Identification of human semiochemicals attractive to the major vectors of onchocerciasis.

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Young, Ryan M; Burkett-Cadena, Nathan D; McGaha, Tommy W; Rodriguez-Perez, Mario A; Toé, Laurent D; Adeleke, Monsuru A; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L; Salinas-Carmona, Mario C; Baker, Bill; Unnasch, Thomas R; Cupp, Eddie W

2015-01-01

Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa.

Myosin7a deficiency results in reduced retinal activity which is improved by gene therapy.

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Pasqualina Colella

Full Text Available Mutations in MYO7A cause autosomal recessive Usher syndrome type IB (USH1B, one of the most frequent conditions that combine severe congenital hearing impairment and retinitis pigmentosa. A promising therapeutic strategy for retinitis pigmentosa is gene therapy, however its pre-clinical development is limited by the mild retinal phenotype of the shaker1 (sh1(-/- murine model of USH1B which lacks both retinal functional abnormalities and degeneration. Here we report a significant, early-onset delay of sh1(-/- photoreceptor ability to recover from light desensitization as well as a progressive reduction of both b-wave electroretinogram amplitude and light sensitivity, in the absence of significant loss of photoreceptors up to 12 months of age. We additionally show that subretinal delivery to the sh1(-/- retina of AAV vectors encoding the large MYO7A protein results in significant improvement of sh1(-/- photoreceptor and retinal pigment epithelium ultrastructural anomalies which is associated with improvement of recovery from light desensitization. These findings provide new tools to evaluate the efficacy of experimental therapies for USH1B. In addition, although AAV vectors expressing large genes might have limited clinical applications due to their genome heterogeneity, our data show that AAV-mediated MYO7A gene transfer to the sh1(-/- retina is effective.

The Expression of the Zonula Adhaerens Protein PLEKHA7 Is Strongly Decreased in High Grade Ductal and Lobular Breast Carcinomas.

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Jean-Christophe Tille

Full Text Available PLEKHA7 is a junctional protein, which participates in a complex that stabilizes E-cadherin at the zonula adhaerens. Since E-cadherin is involved in epithelial morphogenesis, signaling, and tumor progression, we explored PLEKHA7 expression in cancer. PLEKHA7 expression was assessed in invasive ductal and lobular carcinomas of the breast by immunohistochemistry, immunofluorescence and quantitative RT-PCR. PLEKHA7 was detected at epithelial junctions of normal mammary ducts and lobules, and of tubular and micropapillary structures within G1 and G2 ductal carcinomas. At these junctions, the localization of PLEKHA7 was along the circumferential belt (zonula adhaerens, and only partially overlapping with that of E-cadherin, p120ctn and ZO-1, as shown previously in rodent tissues. PLEKHA7 immunolabeling was strongly decreased in G3 ductal carcinomas and undetectable in lobular carcinomas. PLEKHA7 mRNA was detected in both ductal and lobular carcinomas, with no observed correlation between mRNA levels and tumor type or grade. In summary, PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas, and since PLEKHA7 protein but not mRNA expression is strongly decreased or lost in high grade ductal carcinomas and in lobular carcinomas, loss of PLEKHA7 is a newly characterized feature of these carcinomas.

Cdk7 Is Required for Activity-Dependent Neuronal Gene Expression, Long-Lasting Synaptic Plasticity and Long-Term Memory

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Guiqin He

2017-11-01

Full Text Available In the brain, de novo gene expression driven by learning-associated neuronal activities is critical for the formation of long-term memories. However, the signaling machinery mediating neuronal activity-induced gene expression, especially the rapid transcription of immediate-early genes (IEGs remains unclear. Cyclin-dependent kinases (Cdks are a family of serine/threonine kinases that have been firmly established as key regulators of transcription processes underling coordinated cell cycle entry and sequential progression in nearly all types of proliferative cells. Cdk7 is a subunit of transcriptional initiation factor II-H (TFIIH and the only known Cdk-activating kinase (CAK in metazoans. Recent studies using a novel Cdk7 specific covalent inhibitor, THZ1, revealed important roles of Cdk7 in transcription regulation in cancer cells. However, whether Cdk7 plays a role in the regulation of transcription in neurons remains unknown. In this study, we present evidence demonstrating that, in post-mitotic neurons, Cdk7 activity is positively correlated with neuronal activities in cultured primary neurons, acute hippocampal slices and in the brain. Cdk7 inhibition by THZ1 significantly suppressed mRNA levels of IEGs, selectively impaired long-lasting synaptic plasticity induced by 4 trains of high frequency stimulation (HFS and prevented the formation of long-term memories.

Diversity of Pol IV function is defined by mutations at the maize rmr7 locus.

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Jennifer L Stonaker

2009-11-01

Full Text Available Mutations affecting the heritable maintenance of epigenetic states in maize identify multiple small RNA biogenesis factors including NRPD1, the largest subunit of the presumed maize Pol IV holoenzyme. Here we show that mutations defining the required to maintain repression7 locus identify a second RNA polymerase subunit related to Arabidopsis NRPD2a, the sole second largest subunit shared between Arabidopsis Pol IV and Pol V. A phylogenetic analysis shows that, in contrast to representative eudicots, grasses have retained duplicate loci capable of producing functional NRPD2-like proteins, which is indicative of increased RNA polymerase diversity in grasses relative to eudicots. Together with comparisons of rmr7 mutant plant phenotypes and their effects on the maintenance of epigenetic states with parallel analyses of NRPD1 defects, our results imply that maize utilizes multiple functional NRPD2-like proteins. Despite the observation that RMR7/NRPD2, like NRPD1, is required for the accumulation of most siRNAs, our data indicate that different Pol IV isoforms play distinct roles in the maintenance of meiotically-heritable epigenetic information in the grasses.

Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline.

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Utoh, Masahiro; Murayama, Norie; Uno, Yasuhiro; Onose, Yui; Hosaka, Shinya; Fujino, Hideki; Shimizu, Makiko; Iwasaki, Kazuhide; Yamazaki, Hiroshi

2013-12-01

Caffeine (1,3,7-trimethylxanthine) is a phenotyping substrate for human cytochrome P450 1A2. 3-N-Demethylation of caffeine is the main human metabolic pathway, whereas monkeys extensively mediate the 7-N-demethylation of caffeine to form pharmacological active theophylline. Roles of monkey P450 enzymes in theophylline formation from caffeine were investigated using individual monkey liver microsomes and 14 recombinantly expressed monkey P450 enzymes, and the results were compared with those for human P450 enzymes. Caffeine 7-N-demethylation activity in microsomes from 20 monkey livers was not strongly inhibited by α-naphthoflavone, quinidine or ketoconazole, and was roughly correlated with diclofenac 4'-hydroxylation activities. Monkey P450 2C9 had the highest activity for caffeine 7-N-demethylation. Kinetic analysis revealed that monkey P450 2C9 had a high Vmax/Km value for caffeine 7-N-demethylation, comparable to low Km value for monkey liver microsomes. Caffeine could dock favorably with monkey P450 2C9 modeled for 7-N-demethylation and with human P450 1A2 for 3-N-demethylation. The primary metabolite theophylline was oxidized to 8-hydroxytheophylline in similar ways by liver microsomes and by recombinant P450s in both humans and monkeys. These results collectively suggest a high activity for monkey liver P450 2C9 toward caffeine 7-N-demethylation, whereas, in humans, P450 1A2-mediated caffeine 3-N-demethylation is dominant.

Glutamine 57 at the complementary binding site face is a key determinant of morantel selectivity for {alpha}7 nicotinic receptors.

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Bartos, Mariana; Price, Kerry L; Lummis, Sarah C R; Bouzat, Cecilia

2009-08-07

Nicotinic receptors (AChRs) play key roles in synaptic transmission. We explored activation of neuronal alpha7 and mammalian muscle AChRs by morantel and oxantel. Our results revealed a novel action of morantel as a high efficacy and more potent agonist than ACh of alpha7 receptors. The EC(50) for activation by morantel of both alpha7 and alpha7-5HT(3A) receptors is 7-fold lower than that determined for ACh. The minimum morantel concentration required to activate alpha7-5HT(3A) channels is 6-fold lower than that of ACh, and activation episodes are more prolonged than in the presence of ACh. By contrast, oxantel is a weak agonist of alpha7 and alpha7-5HT(3A), and both drugs are very low efficacy agonists of muscle AChRs. The replacement of Gln(57) in alpha7 by glycine, which is found in the equivalent position of the muscle AChR, decreases the efficacy for activation and turns morantel into a partial agonist. The reverse mutation in the muscle AChR (epsilonG57Q) increases 7-fold the efficacy of morantel. The mutations do not affect activation by ACh or oxantel, indicating that this position is selective for morantel. In silico studies show that the tetrahydropyrimidinyl group, common to both drugs, is close to Trp(149) of the principal face of the binding site, whereas the other cyclic group is proximal to Gln(57) of the complementary face in morantel but not in oxantel. Thus, position 57 at the complementary face is a key determinant of the high selectivity of morantel for alpha7. These results provide new information for further progress in drug design.

A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits.

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Leiser, Steven C; Bowlby, Mark R; Comery, Thomas A; Dunlop, John

2009-06-01

Cognition, memory, and attention and arousal have been linked to nicotinic acetylcholine receptors (nAChRs). Thus it is not surprising that nAChRs have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular the alpha7 (alpha7) nAChR has been closely linked with normalization of P50 auditory evoked potential (AEP) gating deficits, and to a lesser extent improvements in pre-pulse inhibition (PPI) of the acoustic startle response. These two brain phenomena can be considered as pre-attentive, occurring while sensory information is being processed, and are important endophenotypes in schizophrenia with deficits likely contributing to the cognitive fragmentation associated with the disease. In addition alpha7 nAChRs have been implicated in attention, in particular under high attentional demand, and in more demanding working memory tasks such as long delays in delayed matching tasks. Efficacy of alpha7 nAChR agonists across a range of cognitive processes ranging from pre-attentive to attentive states and working and recognition memory provides a solid basis for their pro-cognitive effects. This review will focus on the recent work highlighting the role of alpha7 in cognition and cognitive processes.

Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor prognosis in hepatocellular carcinoma.

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An, Jun; Liu, Zhiyong; Liang, Qiong; Pan, Yuhang; Li, Haifeng; Wang, Ruizhi; Jin, Yi

2017-09-01

The expression of Rabl3 and Cullin7 is relevant to the carcinogenesis of certain cancers. However, the relationship of this expression with hepatocellular carcinoma remains unclear. To study the protein expression of Rabl3 and Cullin7 and to evaluate their role in hepatocarcinogenesis, in 162 cases of hepatocellular carcinoma, we used immunohistochemistry to investigate the expression of Rabl3 and Cullin7 in both the cancer tissues and the normal hepatic tissues around the hepatocellular carcinoma. The results demonstrated that the rates of positive Rabl3 and Cullin7 expression were 80.2% and 69.1%, respectively, in hepatocellular carcinoma tissues. However, the rates of positive Rabl3 and Cullin7 expression were 31.5% and 29.0%, respectively, in adjacent normal hepatic tissues. Rabl3 and Cullin7 were expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent normal hepatic tissues (Phepatocellular carcinoma tissues of patients with lymph node metastasis, tumor thrombi in the portal vein and an advanced clinical stage (Phepatocellular carcinoma cohort. Moreover, patients with positive expression for both Rabl3 and Cullin7 had a remarkably shorter survival time compared with patients with negative expression for both proteins (Phepatocellular carcinoma and could be used as a prognostic indicator in patients with hepatocellular carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

7-Dehydrocholesterol (7-DHC), But Not Cholesterol, Causes Suppression of Canonical TGF-β Signaling and Is Likely Involved in the Development of Atherosclerotic Cardiovascular Disease (ASCVD).

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Huang, Shuan Shian; Liu, I-Hua; Chen, Chun-Lin; Chang, Jia-Ming; Johnson, Frank E; Huang, Jung San

2017-06-01

For several decades, cholesterol has been thought to cause ASCVD. Limiting dietary cholesterol intake has been recommended to reduce the risk of the disease. However, several recent epidemiological studies do not support a relationship between dietary cholesterol and/or blood cholesterol and ASCVD. Consequently, the role of cholesterol in atherogenesis is now uncertain. Much evidence indicates that TGF-β, an anti-inflammatory cytokine, protects against ASCVD and that suppression of canonical TGF-β signaling (Smad2-dependent) is involved in atherogenesis. We had hypothesized that cholesterol causes ASCVD by suppressing canonical TGF-β signaling in vascular endothelium. To test this hypothesis, we determine the effects of cholesterol, 7-dehydrocholesterol (7-DHC; the biosynthetic precursor of cholesterol), and other sterols on canonical TGF-β signaling. We use Mv1Lu cells (a model cell system for studying TGF-β activity) stably expressing the Smad2-dependent luciferase reporter gene. We demonstrate that 7-DHC (but not cholesterol or other sterols) effectively suppresses the TGF-β-stimulated luciferase activity. We also demonstrate that 7-DHC suppresses TGF-β-stimulated luciferase activity by promoting lipid raft/caveolae formation and subsequently recruiting cell-surface TGF-β receptors from non-lipid raft microdomains to lipid rafts/caveolae where TGF-β receptors become inactive in transducing canonical signaling and undergo rapid degradation upon TGF-β binding. We determine this by cell-surface 125 I-TGF-β-cross-linking and sucrose density gradient ultracentrifugation. We further demonstrate that methyl-β-cyclodextrin (MβCD), a sterol-chelating agent, reverses 7-DHC-induced suppression of TGF-β-stimulated luciferase activity by extrusion of 7-DHC from resident lipid rafts/caveolae. These results suggest that 7-DHC, but not cholesterol, promotes lipid raft/caveolae formation, leading to suppression of canonical TGF-β signaling and atherogenesis. J

Progress toward elimination of onchocerciasis in the Americas - 1993-2012.

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2013-05-24

Onchocerciasis (river blindness) is caused by the parasitic worm Onchocerca volvulus, transmitted to humans by the bite of infected black flies of the genus Simulium, and is characterized by chronic skin disease, severe itching, and eye lesions that can progress to complete blindness. Currently, among approximately 123 million persons at risk for infection in 38 endemic countries, at least 25.7 million are infected, and 1 million are blinded or have severe visual impairment. Periodic, communitywide mass drug administration (MDA) with ivermectin (Mectizan, Merck) prevents eye and skin disease and might interrupt transmission of the infection, depending on the coverage, duration, and frequency of MDA. The Onchocerciasis Elimination Program for the Americas (OEPA) was launched in response to a 1991 resolution of the Pan American Health Organization (PAHO) calling for the elimination of onchocerciasis from the Americas. By the end of 2012, transmission of the infection, judged by surveys following World Health Organization (WHO) guidelines, had been interrupted or eliminated in four of the six endemic countries in the WHO Americas Region. Thus, in 2013, only 4% (23,378) of the 560,911 persons originally at risk in the Americas will be under ivermectin MDA. Active transmission currently is limited to two foci among Yanomami indigenes in adjacent border areas of Venezuela and Brazil.

7 CFR 981.7 - Edible kernel.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Edible kernel. 981.7 Section 981.7 Agriculture... Regulating Handling Definitions § 981.7 Edible kernel. Edible kernel means a kernel, piece, or particle of almond kernel that is not inedible. [41 FR 26852, June 30, 1976] ...

Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

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Watanabe, Takahiro; Kawamura, Tatsuyoshi; Jacob, Sharon E; Aquilino, Elisabeth A; Orenstein, Jan M; Black, Jodi B; Blauvelt, Andrew

2002-10-01

Pityriasis rosea is a common skin disease that has been suspected to have a viral etiology. We performed nested polymerase chain reaction to detect human herpesvirus-7, human herpesvirus-6, and cytomegalovirus DNA in lesional skin, nonlesional skin, peripheral blood mononuclear cells, serum, and saliva samples isolated from 14 pityriasis rosea patients. Viral mRNA expression and virion visualization within lesional skin were studied by in situ hybridization and transmission electron microscopy, respectively. By nested polymerase chain reaction, human herpesvirus-7 DNA was present in lesional skin (93%), nonlesional skin (86%), saliva (100%), peripheral blood mononuclear cells (83%), and serum (100%) samples, whereas human herpesvirus-6 DNA was detected in lesional skin (86%), nonlesional skin (79%), saliva (80%), peripheral blood mononuclear cells (83%), and serum (88%) samples. By contrast, cytomegalovirus DNA was not detected in these tissues. Control samples from 12 healthy volunteers and 10 psoriasis patients demonstrated rare positivity for either human herpesvirus-7 or human herpesvirus-6 DNA in skin or serum. By in situ hybridization, infiltrating mononuclear cells expressing human herpesvirus-7 and human herpesvirus-6 mRNA were identified in perivascular and periappendageal areas in 100% and 75% pityriasis rosea skin lesions, respectively, compared to herpesviral mRNA positivity in only 13% normal skin and psoriasis skin controls. Transmission electron microscopy failed to reveal herpesviral virions in pityriasis rosea lesional skin. Nested polymerase chain reaction and in situ hybridization enabled detection of human herpesvirus-7 and human herpesvirus-6 in skin and other tissues isolated from patients with pityriasis rosea. These results suggest that pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor β1a (TGFβ1a).

Science.gov (United States)

Turpeinen, Hannu; Oksanen, Anna; Kivinen, Virpi; Kukkurainen, Sampo; Uusimäki, Annemari; Rämet, Mika; Parikka, Mataleena; Hytönen, Vesa P; Nykter, Matti; Pesu, Marko

2013-12-20

Proprotein convertase subtilisin/kexin (PCSK) enzymes convert proproteins into bioactive end products. Although other PCSK enzymes are known to be essential for biological processes ranging from cholesterol metabolism to host defense, the in vivo importance of the evolutionarily ancient PCSK7 has remained enigmatic. Here, we quantified the expressions of all pcsk genes during the 1st week of fish development and in several tissues. pcsk7 expression was ubiquitous and evident already during the early development. To compare mammalian and zebrafish PCSK7, we prepared homology models, which demonstrated remarkable structural conservation. When the PCSK7 function in developing larvae was inhibited, we found that PCSK7-deficient fish have defects in various organs, including the brain, eye, and otic vesicle, and these result in mortality within 7 days postfertilization. A genome-wide analysis of PCSK7-dependent gene expression showed that, in addition to developmental processes, several immune system-related pathways are also regulated by PCSK7. Specifically, the PCSK7 contributed to the mRNA expression and proteolytic cleavage of the cytokine TGFβ1a. Consequently, tgfβ1a morphant fish displayed phenotypical similarities with pcsk7 morphants, underscoring the importance of this cytokine in the zebrafish development. Targeting PCSK activity has emerged as a strategy for treating human diseases. Our results suggest that inhibiting PCSK7 might interfere with normal vertebrate development.

Regulation of calretinin in malignant mesothelioma is mediated by septin 7 binding to the CALB2 promoter.

Science.gov (United States)

Blum, Walter; Pecze, László; Rodriguez, Janine Wörthmüller; Steinauer, Martine; Schwaller, Beat

2018-04-27

The calcium-binding protein calretinin (gene name: CALB2) is currently considered as the most sensitive and specific marker for the diagnosis of malignant mesothelioma (MM). MM is a very aggressive tumor strongly linked to asbestos exposure and with no existing cure so far. The mechanisms of calretinin regulation, as well as its distinct function in MM are still poorly understood. We searched for transcription factors binding to the CALB2 promoter and modulating calretinin expression. For this, DNA-binding assays followed by peptide shotgun-mass spectroscopy analyses were used. CALB2 promoter activity was assessed by dual-luciferase reporter assays. Furthermore, we analyzed the effects of CALB2 promoter-binding proteins by lentiviral-mediated overexpression or down-regulation of identified proteins in MM cells. The modulation of expression of such proteins by butyrate was determined by subsequent Western blot analysis. Immunohistochemical analysis of embryonic mouse lung tissue served to verify the simultaneous co-expression of calretinin and proteins interacting with the CALB2 promoter during early development. Finally, direct interactions of calretinin with target proteins were evidenced by co-immunoprecipitation experiments. Septin 7 was identified as a butyrate-dependent transcription factor binding to a CALB2 promoter region containing butyrate-responsive elements (BRE) resulting in decreased calretinin expression. Accordingly, septin 7 overexpression decreased calretinin expression levels in MM cells. The regulation was found to operate bi-directionally, i.e. calretinin overexpression also decreased septin 7 levels. During murine embryonic development calretinin and septin 7 were found to be co-expressed in embryonic mesenchyme and undifferentiated mesothelial cells. In MM cells, calretinin and septin 7 colocalized during cytokinesis in distinct regions of the cleavage furrow and in the midbody region of mitotic cells. Co-immunoprecipitation experiments

The Escherichia coli COG1738 Member YhhQ Is Involved in 7-Cyanodeazaguanine (preQ0 Transport

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Rémi Zallot

2017-02-01

Full Text Available Queuosine (Q is a complex modification of the wobble base in tRNAs with GUN anticodons. The full Q biosynthesis pathway has been elucidated in Escherichia coli. FolE, QueD, QueE and QueC are involved in the conversion of guanosine triphosphate (GTP to 7-cyano-7-deazaguanine (preQ0, an intermediate of increasing interest for its central role in tRNA and DNA modification and secondary metabolism. QueF then reduces preQ0 to 7-aminomethyl-7-deazaguanine (preQ1. PreQ1 is inserted into tRNAs by tRNA guanine(34 transglycosylase (TGT. The inserted base preQ1 is finally matured to Q by two additional steps involving QueA and QueG or QueH. Most Eubacteria harbor the full set of Q synthesis genes and are predicted to synthesize Q de novo. However, some bacteria only encode enzymes involved in the second half of the pathway downstream of preQ0 synthesis, including the signature enzyme TGT. Different patterns of distribution of the queF, tgt, queA and queG or queH genes are observed, suggesting preQ0, preQ1 or even the queuine base being salvaged in specific organisms. Such salvage pathways require the existence of specific 7-deazapurine transporters that have yet to be identified. The COG1738 family was identified as a candidate for a missing preQ0/preQ1 transporter in prokaryotes, by comparative genomics analyses. The existence of Q precursor salvage was confirmed for the first time in bacteria, in vivo, through an indirect assay. The involvement of the COG1738 in salvage of a Q precursor was experimentally validated in Escherichia coli, where it was shown that the COG1738 family member YhhQ is essential for preQ0 transport.

7 CFR 170.5 - Is there a fee to participate in the USDA Farmers Market?

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Is there a fee to participate in the USDA Farmers... (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.5 Is there a fee to participate in the USDA Farmers Market? No, there are no fees charged to...

Hair growth is promoted by BeauTop via expression of EGF and FGF‑7.

Science.gov (United States)

Lee, Chien-Ying; Yang, Chi-Yu; Lin, Ching-Che; Yu, Min-Chien; Sheu, Shuenn-Jyi; Kuan, Yu-Hsiang

2018-06-01

Minoxidil and finasteride have been approved to treat hair loss by the Food and Drug Administration. However, the further elucidation of treatments for hair loss, including those using Chinese herbal medicine, remains important clinically. BeauTop (BT) is a health food supplement which contains Ginseng radix, Astragali radix, Radix Angelicae sinensis, Ligustri fructus, Rehmannia glutinosa and Eclipta prostrata (Linn). Susbsequent to oral administration of BT at 0.6 g/kg/day to wax/rosin‑induced alopecia in C57BL/6 mice, BT significantly induced hair growth at day 8 compared with control treatment (P<0.05). The expression levels of epidermal growth factor (EGF), and fibroblast growth factor (FGF)‑7 were increased compared with control animals on day 8. In contrast, levels of FGF‑5 of the BT group were reduced compared with the control on day 12. There were no effects on the expression of insulin‑like growth factor 1. The results demonstrated that the mechanism of BT improving alopecia is potentially associated with modulation of EGF and FGF‑7 levels. Taken together, it is suggested that BT may have a potential effect of the promotion of hair growth.

Revisión epidemiológica de la Oncocercosis en América Latina

OpenAIRE

Rodríguez C, Guadalupe C; Lizarazo O, Cristian

2010-01-01

La oncocercosis es una enfermedad exclusiva del ser humano, caracterizada por prurito intenso, lesiones dérmicas y daño ocular que puede llegar a la ceguera. Las regiones endémicas están limitadas a zonas con latitud, relieve, temperatura y humedad relativa óptimas para el desarrollo del parásito y el insecto vector. Estas zonas se encuentran en el oeste de África, Yemen y algunos países de América latina. El parásito es transmitido a través de la mordedura de una mosca del género Simulium, q...

CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1α

International Nuclear Information System (INIS)

Esencay, Mine; Sarfraz, Yasmeen; Zagzag, David

2013-01-01

Glioblastomas, the most common and malignant brain tumors of the central nervous system, exhibit high invasive capacity, which hinders effective therapy. Therefore, intense efforts aimed at improved therapeutics are ongoing to delineate the molecular mechanisms governing glioma cell migration and invasion. In order to perform the studies, we employed optimal cell culture methods and hypoxic conditions, lentivirus-mediated knockdown of protein expression, Western Blot analysis, migration assays and immunoprecipitation. We determined statistical significance by unpaired t-test. In this report, we show that U87MG, LN229 and LN308 glioma cells express CXCR7 and that exposure to hypoxia upregulates CXCR7 protein expression in these cell lines. CXCR7-expressing U87MG, LN229 and LN308 glioma cells migrated towards stromal-derived factor (SDF)-1α/CXCL12 in hypoxic conditions in the Boyden chamber assays. While shRNA-mediated knockdown of CXCR7 expression did not affect the migration of any of the three cell lines in normoxic conditions, we observed a reduction in the migration of LN229 and LN308, but not U87MG, glioma cells towards SDF-1α in hypoxic conditions. In addition, knockdown of CXCR7 expression in LN229 and LN308 glioma cells decreased levels of SDF-1α-induced phosphorylation of ERK1/2 and Akt. Inhibiting CXCR4 in LN229 and LN308 glioma cells that were knocked down for CXCR7 did not further reduce migration towards SDF-1α in hypoxic conditions and did not affect the levels of phosphorylated ERK1/2 and Akt. Analysis of immunoprecipitated CXCR4 from LN229 and LN308 glioma cells revealed co-precipitated CXCR7. Taken together, our findings indicate that both CXCR4 and CXCR7 mediate glioma cell migration towards SDF-1α in hypoxic conditions and support the development of therapeutic agents targeting these receptors

Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis.

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Li, Song; Wang, Baolu; Xu, Yan; Zhang, Junjie

2011-02-12

Autotaxin (ATX) is a secreted glycoprotein with the lysophospholipase D (lysoPLD) activity to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. In the present study, we demonstrated that trichostatin A (TSA), a well-known HDAC inhibitor (HDACi), significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer.

The intermuscular 3-7 Hz drive is not affected by distal proprioceptive input in myoclonus-dystonia

NARCIS (Netherlands)

van der Meer, J. N.; Schouten, A. C.; Bour, L. J.; de Vlugt, E.; van Rootselaar, A. F.; van der Helm, F. C. T.; Tijssen, M. A. J.

In dystonia, both sensory malfunctioning and an abnormal intermuscular low-frequency drive of 3-7 Hz have been found, although cause and effect are unknown. It is hypothesized that sensory processing is primarily disturbed and induces this drive. Accordingly, experimenter-controlled sensory input

The intermuscular 3-7 Hz drive is not affected by distal proprioceptive input in myoclonus-dystonia

NARCIS (Netherlands)

van der Meer, J.N.; Schouten, A.C.; Bour, L.J.; de Vlugt, E.; van Rootselaar, A.F.; van der Helm, F.C.T.; Tijssen, M.A.J.

2010-01-01

In dystonia, both sensory malfunctioning and an abnormal intermuscular low-frequency drive of 3-7 Hz have been found, although cause and effect are unknown. It is hypothesized that sensory processing is primarily disturbed and induces this drive. Accordingly, experimenter-controlled sensory input

Identification of Human Semiochemicals Attractive to the Major Vectors of Onchocerciasis

Science.gov (United States)

Young, Ryan M.; Burkett-Cadena, Nathan D.; McGaha, Tommy W.; Rodriguez-Perez, Mario A.; Toé, Laurent D.; Adeleke, Monsuru A.; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R.; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L.; Salinas-Carmona, Mario C.; Baker, Bill; Unnasch, Thomas R.; Cupp, Eddie W.

2015-01-01

Background Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Methodology/Principal Findings Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. Conclusions/Significance The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa. PMID:25569240

Hyper-parenting is negatively associated with physical activity among 7-12year olds.

Science.gov (United States)

Janssen, Ian

2015-04-01

To explore associations between helicopter, little emperor, tiger mom, and concerted cultivation hyper-parenting styles with child physical activity. 724 North American parents of 7-12 year olds completed a survey (May, 2014) that assessed their engagement in the hyper-parenting styles and the frequency that their child played outdoors, walked/bicycled, and played organized sports. Z-scores were generated for each hyper-parenting style and four groups were created: low (1 SD). Outdoor play, active transportation, and organized sport did not differ across helicopter parenting groups. Children in the low little emperor group had higher (Pparenting styles were associated with lower physical activity among 7-12 year olds. Copyright © 2015. Published by Elsevier Inc.

Left cheek bias for emotion perception, but not expression, is established in children aged 3-7 years.

Science.gov (United States)

Lindell, Annukka K; Tenenbaum, Harriet R; Aznar, Ana

2017-01-01

As the left hemiface is controlled by the emotion-dominant right hemisphere, emotion is expressed asymmetrically. Portraits showing a model's left cheek consequently appear more emotive. Though the left cheek bias is well established in adults, it has not been investigated in children. To determine whether the left cheek biases for emotion perception and expression are present and/or develop between the ages of 3 and 7 years, 145 children (71 male, 74 female; M age = 65.49 months) completed two experimental tasks: one assessing biases in emotion perception, and the other assessing biases in emotion expression. Regression analysis confirmed that children aged 3-7 years find left cheek portraits happier than right cheek portraits, and age does not predict the magnitude of the bias. In contrast when asked to pose for a photo expressing happiness children did not show a left cheek bias, with logistic regression confirming that age did not predict posing orientations. These findings indicate that though the left cheek bias for emotion perception is established by age 3, a similar bias for emotion expression is not evident by age 7. This implies that tacit knowledge of the left cheek's greater expressivity is not innate but develops in later childhood/adolescence.

FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients

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Hagedorn Martin

2007-02-01

Full Text Available Abstract Background In the quest for novel molecular mediators of glioma progression, we studied the regulation of FBXW7 (hCDC4/hAGO/SEL10, its association with survival of patients with glioblastoma and its potential role as a tumor suppressor gene in glioma cells. The F-box protein Fbxw7 is a component of SCFFbxw7, a Skp1-Cul1-F-box E3 ubiquitin ligase complex that tags specific proteins for proteasome degradation. FBXW7 is mutated in several human cancers and functions as a haploinsufficient tumor suppressor in mice. Any of the identified targets, Cyclin E, c-Myc, c-Jun, Notch1/4 and Aurora-A may have oncogenic properties when accumulated in tumors with FBXW7 loss. Results We tested the expression of FBXW7 in human glioma biopsies by quantitative PCR and compared the transcript levels of grade IV glioma (glioblastoma, G-IV with those of grade II tumors (G-II. In more than 80% G-IV, expression of FBXW7 was significantly reduced. In addition, levels of FBXW7 were correlated with survival indicating a possible implication in tumor aggressiveness. Locus 4q31.3 which carries FBXW7 was investigated by in situ hybridization on biopsy touchprints. This excluded allelic loss as the principal cause for low expression of FBXW7 in G-IV tumors. Two targets of Fbxw7, Aurora-A and Notch4 were preferentially immunodetected in G-IV biopsies. Next, we investigated the effects of FBXW7 misregulation in glioma cells. U87 cells overexpressing nuclear isoforms of Fbxw7 lose the expression of the proliferation markers PCNA and Ki-67, and get counterselected in vitro. This observation fits well with the hypothesis that Fbxw7 functions as a tumor suppressor in astroglial cells. Finally, FBXW7 knockdown in U87 cells leads to defects in mitosis that may promote aneuploidy in progressing glioma. Conclusion Our results show that FBXW7 expression is a prognostic marker for patients with glioblastoma. We suggest that loss of FBXW7 plays an important role in glioma

Wheat TaRab7 GTPase is part of the signaling pathway in responses to stripe rust and abiotic stimuli.

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Furong Liu

Full Text Available Small GTP-binding proteins function as regulators of specific intercellular fundamental biological processes. In this study, a small GTP-binding protein Rab7 gene, designated as TaRab7, was identified and characterized from a cDNA library of wheat leaves infected with Puccinia striiformis f. sp. tritici (Pst the wheat stripe rust pathogen. The gene was predicted to encode a protein of 206 amino acids, with a molecular mass of 23.13 KDa and an isoeletric point (pI of 5.13. Further analysis revealed the presence of a conserved signature that is characteristic of Rab7, and phylogenetic analysis demonstrated that TaRab7 has the highest similarity to a small GTP binding protein gene (BdRab7-like from Brachypodium distachyon. Quantitative real-time PCR assays revealed that the expression of TaRab7 was higher in the early stage of the incompatible interactions between wheat and Pst than in the compatible interaction, and the transcription level of TaRab7 was also highly induced by environmental stress stimuli. Furthermore, knocking down TaRab7 expression by virus induced gene silencing enhanced the susceptibility of wheat cv. Suwon 11 to an avirulent race CYR23. These results imply that TaRab7 plays an important role in the early stage of wheat-stripe rust fungus interaction and in stress tolerance.

Feedback from visual cortical area 7 to areas 17 and 18 in cats: How neural web is woven during feedback.

Science.gov (United States)

Yang, X; Ding, H; Lu, J

2016-01-15

To investigate the feedback effect from area 7 to areas 17 and 18, intrinsic signal optical imaging combined with pharmacological, morphological methods and functional magnetic resonance imaging (fMRI) was employed. A spatial frequency-dependent decrease in response amplitude of orientation maps was observed in areas 17 and 18 when area 7 was inactivated by a local injection of GABA, or by a lesion induced by liquid nitrogen freezing. The pattern of orientation maps of areas 17 and 18 after the inactivation of area 7, if they were not totally blurred, paralleled the normal one. In morphological experiments, after one point at the shallow layers within the center of the cat's orientation column of area 17 was injected electrophoretically with HRP (horseradish peroxidase), three sequential patches in layers 1, 2 and 3 of area 7 were observed. Employing fMRI it was found that area 7 feedbacks mainly to areas 17 and 18 on ipsilateral hemisphere. Therefore, our conclusions are: (1) feedback from area 7 to areas 17 and 18 is spatial frequency modulated; (2) feedback from area 7 to areas 17 and 18 occurs mainly ipsilaterally; (3) histological feedback pattern from area 7 to area 17 is weblike. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

CXCR4/CXCL12/CXCR7 axis is functional in neuroendocrine tumors and signals on mTOR.

Science.gov (United States)

Circelli, Luisa; Sciammarella, Concetta; Guadagno, Elia; Tafuto, Salvatore; del Basso de Caro, Marialaura; Botti, Giovanni; Pezzullo, Luciano; Aria, Massimo; Ramundo, Valeria; Tatangelo, Fabiana; Losito, Nunzia Simona; Ieranò, Caterina; D'Alterio, Crescenzo; Izzo, Francesco; Ciliberto, Gennaro; Colao, Annamaria; Faggiano, Antongiulio; Scala, Stefania

2016-04-05

To evaluate the possible crosstalk between C-X-C chemokine receptor 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12)/C-X-C chemokine receptor 7 (CXCR7) axis with the mammalian target of rapamycin (mTOR) pathway in neuroendocrine tumors (NETs). Sixty-one human NETs were included into the study. CXCR4/CXCL12/CXCR7 axis and mTOR pathway were assessed by qRT-PCR and immunohistochemistry (IHC). The effect of mTOR inhibitor, RAD001, was evaluated on CXCR4 pathway through proliferation and p-Erk and p-AKT induction. CXCR4/CXCL12/CXCR7 axis and p-mTOR were found to be active and correlated with grading, Ki67 index and tumor stage. mTOR pathway activation significantly correlated with poor prognosis. In human NET cells, CXCL12 induced mTOR signalling while AMD3100 (CXCR4-antagonist) impaired it. The mTOR-antagonist, RAD001, impaired the CXCL12-dependent induction of CXCR4 downstream effectors. Combination of AMD3100 and RAD001 potentiate cell growth inhibition. CXCR4/CXCL12/CXCR7 axis is active in NETs and signals on mTOR. CXCR4 might be considered a prognostic factor in NETs. Combined treatment with AMD3100 and RAD001 may provide clinical benefits in NET patients with drug-resistant.

7Li--7Be experiment

International Nuclear Information System (INIS)

Rowley, J.K.

1978-01-01

An experiment to detect solar neutrinos by use of lithium is considered. The reaction employed is 7 Li(ν,e - ) 7 Be. The parameters of a possible experimental arrangement are described; chemical separation, backgrounds, and counting are discussed at some length. Despite the problems such an experiment still seems feasible. 5 figures, 6 tables

The ADH7 Promoter of Saccharomyces cerevisiae is Vanillin-Inducible and Enables mRNA Translation Under Severe Vanillin Stress.

Science.gov (United States)

Nguyen, Trinh T M; Iwaki, Aya; Izawa, Shingo

2015-01-01

Vanillin is one of the major phenolic aldehyde compounds derived from lignocellulosic biomass and acts as a potent fermentation inhibitor to repress the growth and fermentative ability of yeast. Vanillin can be reduced to its less toxic form, vanillyl alcohol, by the yeast NADPH-dependent medium chain alcohol dehydrogenases, Adh6 and Adh7. However, there is little information available regarding the regulation of their gene expression upon severe vanillin stress, which has been shown to repress the bulk translation activity in yeast cells. Therefore, in this study, we investigated expression patterns of the ADH6 and ADH7 genes in the presence of high concentrations of vanillin. We found that although both genes were transcriptionally upregulated by vanillin stress, they showed different protein expression patterns in response to vanillin. Expression of Adh6 was constitutive and gradually decreased under vanillin stress, whereas expression of Adh7 was inducible, and, importantly, occurred under severe vanillin stress. The null mutants of ADH6 or ADH7 genes were hypersensitive to vanillin and reduced vanillin less efficiently than the wild type, confirming the importance of Adh6 and Adh7 in vanillin detoxification. Additionally, we demonstrate that the ADH7 promoter is vanillin-inducible and enables effective protein synthesis even under severe vanillin stress, and it may be useful for the improvement of vanillin-tolerance and biofuel production efficiency via modification of yeast gene expression in the presence of high concentrations of vanillin.

The ADH7 promoter of Saccharomyces cerevisiae is vanillin-inducible and enables mRNA translation under severe vanillin stress

Directory of Open Access Journals (Sweden)

Trinh Thi My Nguyen

2015-12-01

Full Text Available Vanillin is one of the major phenolic aldehyde compounds derived from lignocellulosic biomass and acts as a potent fermentation inhibitor to repress the growth and fermentative ability of yeast. Vanillin can be reduced to its less toxic form, vanillyl alcohol, by the yeast NADPH-dependent medium chain alcohol dehydrogenases, Adh6 and Adh7. However, there is little information available regarding the regulation of their gene expression upon severe vanillin stress, which has been shown to repress the bulk translation activity in yeast cells. Therefore, in this study, we investigated expression patterns of the ADH6 and ADH7 genes in the presence of high concentrations of vanillin. We found that although both genes were transcriptionally upregulated by vanillin stress, they showed different protein expression patterns in response to vanillin. Expression of Adh6 was constitutive and gradually decreased under vanillin stress, whereas expression of Adh7 was inducible, and, importantly, occurred under severe vanillin stress. The null mutants of ADH6 or ADH7 genes were hypersensitive to vanillin and reduced vanillin less efficiently than the wild type, confirming the importance of Adh6 and Adh7 in vanillin detoxification. Additionally, we demonstrate that the ADH7 promoter is vanillin-inducible and enables effective protein synthesis even under severe vanillin stress, and it may be useful for the improvement of vanillin-tolerance and biofuel production efficiency via modification of yeast gene expression in the presence of high concentrations of vanillin.

Langerhans cell homeostasis and activation is altered in hyperplastic human papillomavirus type 16 E7 expressing epidermis.

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Nor Malia Abd Warif

Full Text Available It has previously been shown that expression of human papillomavirus type 16 (HPV E7 in epidermis causes hyperplasia and chronic inflammation, characteristics of pre-malignant lesions. Importantly, E7-expressing epidermis is strongly immune suppressed and is not rejected when transplanted onto immune competent mice. Professional antigen presenting cells are considered essential for initiation of the adaptive immune response that results in graft rejection. Langerhans cells (LC are the only antigen presenting cells located in normal epidermis and altered phenotype and function of these cells may contribute to the immune suppressive microenvironment. Here, we show that LC are atypically activated as a direct result of E7 expression in the epidermis, and independent of the presence of lymphocytes. The number of LC was significantly increased and the LC are functionally impaired, both in migration and in antigen uptake. However when the LC were extracted from K14E7 skin and matured in vitro they were functionally competent to present and cross-present antigen, and to activate T cells. The ability of the LC to present and cross-present antigen following maturation supports retention of full functional capacity when removed from the hyperplastic skin microenvironment. As such, opportunities are afforded for the development of therapies to restore normal LC function in hyperplastic skin.

Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells.

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Aric L Gregson

2010-06-01

Full Text Available Bronchiolitis obliterans syndrome (BOS is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(-, and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+ and CD103(- and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+ Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+ Treg frequency and inversely with BOS. Higher frequencies of CCR7(+ CD3(+CD4(+CD25(hiFoxp3(+CD45RA(- lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.

25 CFR 513.7 - What is the Commission's policy on revoking a debtor's ability to engage in Indian gaming for...

Science.gov (United States)

2010-04-01

... ability to engage in Indian gaming for failure to pay a debt? 513.7 Section 513.7 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEBT COLLECTION General Provisions § 513.7 What is the Commission's policy on revoking a debtor's ability to engage in Indian gaming for...

The histone demethylase LSD1 is required for estrogen-dependent S100A7 gene expression in human breast cancer cells

International Nuclear Information System (INIS)

Yu, Seung Eun; Jang, Yeun Kyu

2012-01-01

Highlights: ► S100A7 gene is up-regulated in response to estrogen in breast cancer cells. ► Histone demethylase LSD1 can associate physically with S100A7 gene promoters. ► E2-induced S100A7 expression requires the enzymatic activity of LSD1. ► S100A7 inhibits cell proliferation, implying its tumor suppressor-like function. -- Abstract: S100A7, a member of S100 calcium binding protein family, is highly associated with breast cancer. However, the molecular mechanism of S100A7 regulation remains unclear. Here we show that long-term treatment with estradiol stimulated S100A7 expression in MCF7 breast cancer cells at both the transcriptional and translational levels. Both treatment with a histone demethylase LSD1 inhibitor and shRNA-based knockdown of LSD1 expression significantly decreased 17β-estradiol (E2)-induced S100A7 expression. These reduced E2-mediated S100A7 expression are rescued by the overexpressed wild-type LSD1 but not by its catalytically inactive mutant. Our data showed in vivo association of LSD1 with S100A7 promoters, confirming the potential role of LSD1 in regulating S100A7 expression. S100A7 knockdown increased both normal cell growth and estrogen-induced cell proliferation, suggesting a negative influence by S100A7 on the growth of cancer cells. Together, our data suggest that estrogen-induced S100A7 expression mediated by the histone demethylase LSD1 may downregulate breast cancer cell proliferation, implying a potential tumor suppressor-like function for S100A7.

30 CFR 290.7 - Do I have to comply with the decision or order while my appeal is pending?

Science.gov (United States)

2010-07-01

... while my appeal is pending? 290.7 Section 290.7 Mineral Resources MINERALS MANAGEMENT SERVICE... Do I have to comply with the decision or order while my appeal is pending? (a) The decision or order...; or (2) You post a surety bond under 30 CFR 250.1409 pending the appeal challenging an order to pay a...

Nuclear-specific AR-V7 Protein Localization is Necessary to Guide Treatment Selection in Metastatic Castration-resistant Prostate Cancer.

Science.gov (United States)

Scher, Howard I; Graf, Ryon P; Schreiber, Nicole A; McLaughlin, Brigit; Lu, David; Louw, Jessica; Danila, Daniel C; Dugan, Lyndsey; Johnson, Ann; Heller, Glenn; Fleisher, Martin; Dittamore, Ryan

2017-06-01

using an AR-V7 protein biomarker in CTCs, nuclear-specific localization is required. We analyzed outcomes for patients with metastatic castration-resistant prostate cancer on androgen receptor signaling inhibitors and standard chemotherapy. Patients with circulating tumor cells that had AR-V7 protein in the cellular nuclei were very likely to survive longer on taxane-based chemotherapy, and tests unable to distinguish where the protein is located in the cell are not as predictive of benefit. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Inter-domain Synergism Is Required for Efficient Feeding of Cellulose Chain into Active Site of Cellobiohydrolase Cel7A*

OpenAIRE

Kont, Riin; Kari, Jeppe; Borch, Kim; Westh, Peter; Väljamäe, Priit

2016-01-01

Structural polysaccharides like cellulose and chitin are abundant and their enzymatic degradation to soluble sugars is an important route in green chemistry. Processive glycoside hydrolases (GHs), like cellobiohydrolase Cel7A of Trichoderma reesei (TrCel7A) are key components of efficient enzyme systems. TrCel7A consists of a catalytic domain (CD) and a smaller carbohydrate-binding module (CBM) connected through the glycosylated linker peptide. A tunnel-shaped active site rests in the CD and ...

Ozone impedes the ability of a herbivore to find its host

Science.gov (United States)

Fuentes, Jose D.; Roulston, T.'ai H.; Zenker, John

2013-03-01

Plant-emitted hydrocarbons mediate several key interactions between plants and insects. They enhance the ability of pollinators and herbivores to locate suitable host plants, and parasitoids to locate herbivores. While plant volatiles provide strong chemical signals, these signals are potentially degraded by exposure to pollutants such as ozone, which has increased in the troposphere and is projected to continue to increase over the coming decades. Despite the potential broad ecological significance of reduced plant signaling effectiveness, few studies have examined behavioral responses of insects to their hosts in polluted environments. Here, we use a laboratory study to test the effect of ozone concentration gradients on the ability of the striped cucumber beetle (Acalymma vittatum) to locate flowers of its host plant, Cucurbita foetidissima. Y-tube experiments showed that ozone mixing ratios below 80 parts per billion (ppb) resulted in beetles moving toward their host plant, but levels above 80 ppb resulted in beetles moving randomly with respect to host location. There was no evidence that beetles avoided polluted air directly. The results show that ozone pollution has great potential to perniciously alter key interactions between plants and animals.

Ozone impedes the ability of a herbivore to find its host

International Nuclear Information System (INIS)

Fuentes, Jose D; Zenker, John; Roulston, T’ai H

2013-01-01

Plant-emitted hydrocarbons mediate several key interactions between plants and insects. They enhance the ability of pollinators and herbivores to locate suitable host plants, and parasitoids to locate herbivores. While plant volatiles provide strong chemical signals, these signals are potentially degraded by exposure to pollutants such as ozone, which has increased in the troposphere and is projected to continue to increase over the coming decades. Despite the potential broad ecological significance of reduced plant signaling effectiveness, few studies have examined behavioral responses of insects to their hosts in polluted environments. Here, we use a laboratory study to test the effect of ozone concentration gradients on the ability of the striped cucumber beetle (Acalymma vittatum) to locate flowers of its host plant, Cucurbita foetidissima. Y-tube experiments showed that ozone mixing ratios below 80 parts per billion (ppb) resulted in beetles moving toward their host plant, but levels above 80 ppb resulted in beetles moving randomly with respect to host location. There was no evidence that beetles avoided polluted air directly. The results show that ozone pollution has great potential to perniciously alter key interactions between plants and animals. (letter)

Inter-domain synergism is required for efficient feeding of cellulose chain into active site of cellobiohydrolase Cel7A

DEFF Research Database (Denmark)

Kont, Riin; Kari, Jeppe; Borch, Kim

2016-01-01

systems. TrCel7A consists of catalytic domain (CD) and a smaller carbohydrate binding module (CBM) connected through the glycosylated linker peptide. A tunnel shaped active site rests in the CD and contains 10 glucose unit binding sites. The active site of TrCel7A is lined with four Trp residues with two...... to Ala substitution on on-rates was strongly dependent on the presence of the CBM-linker. This compensation between CBM-linker and Trp-38 indicates synergism between CBM-linker and CD in feeding the cellulose chain into the active site. The inter-domain synergism was pre-requisite for the efficient......Structural polysaccharides like cellulose and chitin are abundant and their enzymatic degradation to soluble sugars is an important route in green chemistry. Processive glycoside hydrolases (GHs), like cellobiohydrolase Cel7A of Trichoderma reesei (TrCel7A) are key components of efficient enzyme...

Pdlim7 is required for maintenance of the mesenchymal/epidermal Fgf signaling feedback loop during zebrafish pectoral fin development

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Klosowiak Julian

2010-10-01

Full Text Available Abstract Background Vertebrate limb development involves a reciprocal feedback loop between limb mesenchyme and the overlying apical ectodermal ridge (AER. Several gene pathways participate in this feedback loop, including Fgf signaling. In the forelimb lateral plate mesenchyme, Tbx5 activates Fgf10 expression, which in turn initiates and maintains the mesenchyme/AER Fgf signaling loop. Recent findings have revealed that Tbx5 transcriptional activity is regulated by dynamic nucleocytoplasmic shuttling and interaction with Pdlim7, a PDZ-LIM protein family member, along actin filaments. This Tbx5 regulation is critical in heart formation, but the coexpression of both proteins in other developing tissues suggests a broader functional role. Results Knock-down of Pdlim7 function leads to decreased pectoral fin cell proliferation resulting in a severely stunted fin phenotype. While early gene induction and patterning in the presumptive fin field appear normal, the pectoral fin precursor cells display compaction and migration defects between 18 and 24 hours post-fertilization (hpf. During fin growth fgf24 is sequentially expressed in the mesenchyme and then in the apical ectodermal ridge (AER. However, in pdlim7 antisense morpholino-treated embryos this switch of expression is prevented and fgf24 remains ectopically active in the mesenchymal cells. Along with the lack of fgf24 in the AER, other critical factors including fgf8 are reduced, suggesting signaling problems to the underlying mesenchyme. As a consequence of perturbed AER function in the absence of Pdlim7, pathway components in the fin mesenchyme are misregulated or absent, indicating a breakdown of the Fgf signaling feedback loop, which is ultimately responsible for the loss of fin outgrowth. Conclusion This work provides the first evidence for the involvement of Pdlim7 in pectoral fin development. Proper fin outgrowth requires fgf24 downregulation in the fin mesenchyme with subsequent

USP7 Is a Tumor-Specific WNT Activator for APC-Mutated Colorectal Cancer by Mediating β-Catenin Deubiquitination

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Laura Novellasdemunt

2017-10-01

Full Text Available The tumor suppressor gene adenomatous polyposis coli (APC is mutated in most colorectal cancers (CRCs, resulting in constitutive Wnt activation. To understand the Wnt-activating mechanism of the APC mutation, we applied CRISPR/Cas9 technology to engineer various APC-truncated isogenic lines. We find that the β-catenin inhibitory domain (CID in APC represents the threshold for pathological levels of Wnt activation and tumor transformation. Mechanistically, CID-deleted APC truncation promotes β-catenin deubiquitination through reverse binding of β-TrCP and USP7 to the destruction complex. USP7 depletion in APC-mutated CRC inhibits Wnt activation by restoring β-catenin ubiquitination, drives differentiation, and suppresses xenograft tumor growth. Finally, the Wnt-activating role of USP7 is specific to APC mutations; thus, it can be used as a tumor-specific therapeutic target for most CRCs.

41 CFR 301-50.7 - Should I use the online self-service booking tool once ETS is available within my agency?

Science.gov (United States)

2010-07-01

... SERVICES § 301-50.7 Should I use the online self-service booking tool once ETS is available within my agency? Yes, you should use the online self-service booking tool offered by ETS or your agency's TMS... self-service booking tool once ETS is available within my agency? 301-50.7 Section 301-50.7 Public...

Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

Science.gov (United States)

Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

2017-07-12

Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A tryptophan-rich motif in the human parainfluenza virus type 2 V protein is critical for the blockade of toll-like receptor 7 (TLR7)- and TLR9-dependent signaling.

Science.gov (United States)

Kitagawa, Yoshinori; Yamaguchi, Mayu; Zhou, Min; Komatsu, Takayuki; Nishio, Machiko; Sugiyama, Tsuyoshi; Takeuchi, Kenji; Itoh, Masae; Gotoh, Bin

2011-05-01

Plasmacytoid dendritic cells (pDCs) do not produce alpha interferon (IFN-α) unless viruses cause a systemic infection or overcome the first-line defense provided by conventional DCs and macrophages. We show here that even paramyxoviruses, whose infections are restricted to the respiratory tract, have a V protein able to prevent Toll-like receptor 7 (TLR7)- and TLR9-dependent IFN-α induction specific to pDCs. Mutational analysis of human parainfluenza virus type 2 demonstrates that the second Trp residue of the Trp-rich motif (Trp-X(3)-Trp-X(9)-Trp) in the C-terminal domain unique to V, a determinant for IRF7 binding, is critical for the blockade of TLR7/9-dependent signaling.

Molecular and Cytological Comparisons of Chromosomes 7el₁, 7el₂, 7E(e), and 7E ⁱ Derived from Thinopyrum.

Science.gov (United States)

Guo, Jun; He, Fang; Cai, Jin-Jin; Wang, Hong-Wei; Li, An-Fei; Wang, Hong-Gang; Kong, Ling-Rang

2015-01-01

Thinopyrum chromosomes 7el1, 7el2, 7E(e), and 7E(i), homoeologous to group 7 chromosomes of common wheat (Triticum aestivum), were determined to have many useful agronomical traits for wheat improvement. To analyze the genetic relationships among the 4 Thinopyrum 7E chromosomes, the conserved orthologous set markers, genomic in situ hybridization (GISH), and meiotic chromosome pairing were used in this study. The unweighted pair-group method with arithmetical averages (UPGMA) analysis indicated that 7el1, derived from T. ponticum, and 7E(i), derived from T. intermedium, were the most closely related. 7el2, derived from T. ponticum, was relatively distant from the 7el1-7E(i) complex. While 7E(e), derived from T. elongatum, was more distantly related to 7el1, 7el2, and 7E(i). This is the first report showing that 7el1 and 7E(i) may be similar, which could be explained by the similar chromosome signal distribution revealed by GISH as well as UPGMA analysis revealed by both molecular markers and the highest frequency of meiotic pairing. The newly developed genome-specific molecular markers may be useful for marker-assisted selection of Lr19, Bdv3, and Fhblop. © 2015 S. Karger AG, Basel.

Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia.

Science.gov (United States)

Mulle, Jennifer Gladys; Pulver, Ann E; McGrath, John A; Wolyniec, Paula S; Dodd, Anne F; Cutler, David J; Sebat, Jonathan; Malhotra, Dheeraj; Nestadt, Gerald; Conrad, Donald F; Hurles, Matthew; Barnes, Chris P; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F; Gejman, Pablo V; Sanders, Alan R; Duan, Jubao; Mitchell, Adele A; Peter, Inga; Sklar, Pamela; O'Dushlaine, Colm T; Grozeva, Detelina; O'Donovan, Michael C; Owen, Michael J; Hultman, Christina M; Kähler, Anna K; Sullivan, Patrick F; Kirov, George; Warren, Stephen T

2014-03-01

Several copy number variants (CNVs) have been implicated as susceptibility factors for schizophrenia (SZ). Some of these same CNVs also increase risk for autism spectrum disorders, suggesting an etiologic overlap between these conditions. Recently, de novo duplications of a region on chromosome 7q11.23 were associated with autism spectrum disorders. The reciprocal deletion of this region causes Williams-Beuren syndrome. We assayed an Ashkenazi Jewish cohort of 554 SZ cases and 1014 controls for genome-wide CNV. An excess of large rare and de novo CNVs were observed, including a 1.4 Mb duplication on chromosome 7q11.23 identified in two unrelated patients. To test whether this 7q11.23 duplication is also associated with SZ, we obtained data for 14,387 SZ cases and 28,139 controls from seven additional studies with high-resolution genome-wide CNV detection. We performed a meta-analysis, correcting for study population of origin, to assess whether the duplication is associated with SZ. We found duplications at 7q11.23 in 11 of 14,387 SZ cases with only 1 in 28,139 control subjects (unadjusted odds ratio 21.52, 95% confidence interval: 3.13-922.6, p value 5.5 × 10(-5); adjusted odds ratio 10.8, 95% confidence interval: 1.46-79.62, p value .007). Of three SZ duplication carriers with detailed retrospective data, all showed social anxiety and language delay premorbid to SZ onset, consistent with both human studies and animal models of the 7q11.23 duplication. We have identified a new CNV associated with SZ. Reciprocal duplication of the Williams-Beuren syndrome deletion at chromosome 7q11.23 confers an approximately tenfold increase in risk for SZ. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The novel human influenza A(H7N9) virus is naturally adapted to efficient growth in human lung tissue.

Science.gov (United States)

Knepper, Jessica; Schierhorn, Kristina L; Becher, Anne; Budt, Matthias; Tönnies, Mario; Bauer, Torsten T; Schneider, Paul; Neudecker, Jens; Rückert, Jens C; Gruber, Achim D; Suttorp, Norbert; Schweiger, Brunhilde; Hippenstiel, Stefan; Hocke, Andreas C; Wolff, Thorsten

2013-10-08

A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients. Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to

miR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7

International Nuclear Information System (INIS)

Zhou, Chuanyi; Shen, Liangfang; Mao, Lei; Wang, Bing; Li, Yang; Yu, Huizhi

2015-01-01

MicroRNAs (miRNAs) are involved in the cervical carcinogenesis and progression. In this study, we investigated the role of miR-92a in progression and invasion of cervical cancer. MiR-92a was significantly upregulated in cervical cancer tissues and cell lines. Overexpression of miR-92a led to remarkably enhanced proliferation by promoting cell cycle transition from G1 to S phase and significantly enhanced invasion of cervical cancer cells, while its knockdown significantly reversed these cellular events. Bioinformatics analysis suggested F-box and WD repeat domain-containing 7 (FBXW7) as a novel target of miR-92a, and miR-92a suppressed the expression level of FBXW7 mRNA by direct binding to its 3′-untranslated region (3′UTR). Expression of miR-92a was negatively correlated with FBXW7 in cervical cancer tissues. Furthermore, Silencing of FBXW7 counteracted the effects of miR-92a suppression, while its overexpression reversed oncogenic effects of miR-92a. Together, these findings indicate that miR-92a acts as an onco-miRNA and may contribute to the progression and invasion of cervical cancer, suggesting miR-92a as a potential novel diagnostic and therapeutic target of cervical cancer. - Highlights: • miR-92a is elevated in cervical cancer tissues and cell lines. • miR-92a promotes cervical cancer cell proliferation, cell cycle transition from G1 to S phase and invasion. • FBXW7 is a direct target of miR-92a. • FBXW7 counteracts the oncogenic effects of miR-92a on cervical cancer cells

C-terminal phenylalanine of bacteriophage T7 single-stranded DNA-binding protein is essential for strand displacement synthesis by T7 DNA polymerase at a nick in DNA.

Science.gov (United States)

Ghosh, Sharmistha; Marintcheva, Boriana; Takahashi, Masateru; Richardson, Charles C

2009-10-30

Single-stranded DNA-binding protein (gp2.5), encoded by gene 2.5 of bacteriophage T7, plays an essential role in DNA replication. Not only does it remove impediments of secondary structure in the DNA, it also modulates the activities of the other replication proteins. The acidic C-terminal tail of gp2.5, bearing a C-terminal phenylalanine, physically and functionally interacts with the helicase and DNA polymerase. Deletion of the phenylalanine or substitution with a nonaromatic amino acid gives rise to a dominant lethal phenotype, and the altered gp2.5 has reduced affinity for T7 DNA polymerase. Suppressors of the dominant lethal phenotype have led to the identification of mutations in gene 5 that encodes the T7 DNA polymerase. The altered residues in the polymerase are solvent-exposed and lie in regions that are adjacent to the bound DNA. gp2.5 lacking the C-terminal phenylalanine has a lower affinity for gp5-thioredoxin relative to the wild-type gp2.5, and this affinity is partially restored by the suppressor mutations in DNA polymerase. gp2.5 enables T7 DNA polymerase to catalyze strand displacement DNA synthesis at a nick in DNA. The resulting 5'-single-stranded DNA tail provides a loading site for T7 DNA helicase. gp2.5 lacking the C-terminal phenylalanine does not support this event with wild-type DNA polymerase but does to a limited extent with T7 DNA polymerase harboring the suppressor mutations.

C-terminal Phenylalanine of Bacteriophage T7 Single-stranded DNA-binding Protein Is Essential for Strand Displacement Synthesis by T7 DNA Polymerase at a Nick in DNA*

Science.gov (United States)

Ghosh, Sharmistha; Marintcheva, Boriana; Takahashi, Masateru; Richardson, Charles C.

2009-01-01

Single-stranded DNA-binding protein (gp2.5), encoded by gene 2.5 of bacteriophage T7, plays an essential role in DNA replication. Not only does it remove impediments of secondary structure in the DNA, it also modulates the activities of the other replication proteins. The acidic C-terminal tail of gp2.5, bearing a C-terminal phenylalanine, physically and functionally interacts with the helicase and DNA polymerase. Deletion of the phenylalanine or substitution with a nonaromatic amino acid gives rise to a dominant lethal phenotype, and the altered gp2.5 has reduced affinity for T7 DNA polymerase. Suppressors of the dominant lethal phenotype have led to the identification of mutations in gene 5 that encodes the T7 DNA polymerase. The altered residues in the polymerase are solvent-exposed and lie in regions that are adjacent to the bound DNA. gp2.5 lacking the C-terminal phenylalanine has a lower affinity for gp5-thioredoxin relative to the wild-type gp2.5, and this affinity is partially restored by the suppressor mutations in DNA polymerase. gp2.5 enables T7 DNA polymerase to catalyze strand displacement DNA synthesis at a nick in DNA. The resulting 5′-single-stranded DNA tail provides a loading site for T7 DNA helicase. gp2.5 lacking the C-terminal phenylalanine does not support this event with wild-type DNA polymerase but does to a limited extent with T7 DNA polymerase harboring the suppressor mutations. PMID:19726688

The utility of cytokeratins 7 and 20 (CK7/20 immunohistochemistry in the distinction of short-segment Barrett esophagus from gastric intestinal metaplasia: Is it reliable?

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Bakirci Nadi

2003-12-01

Full Text Available Abstract Background The purpose of the present correlative immunohistochemical study was to assess the utility of cytokeratin (CK7 and CK20 expression in the diagnosis of short-segment Barrett esophagus, particularly its efficacy in differentiating Barrett mucosa from intestinal metaplasia of the gastric cardia and corpus. Methods Two groups of endoscopic biopsy specimens were examined, including 20 endoscopic biopsy specimens of short-segment Barrett esophagus (Group A and equal number exhibiting Helicobacter pylori associated intestinal metaplasia of the gastric cardia and corpus (Group B. All were investigated by immunohistochemistry using the standard ABC method for CK7 and CK20 expression. Fisher's exact test was used for statistical analysis of Barrett CK7/20 and gastric CK7/20 patterns between the groups. Results The anticipated pattern of reactivity in Barrett mucosa (CK7: strong diffuse positivity in superficial and deep glands; CK20: positivity in surface epithelium and superficial glands was seen in 2 cases of Group A specimens. The expected gastric pattern (CK7: patchy immunostaining with variable involvement of deep glands; CK20: patchy immunostaining of superficial and deep glands in incomplete intestinal metaplasia / absence of CK7 immunoreactivity with strong CK20 staining in superficial and deep glands in complete intestinal metaplasia was seen in 8 cases of Group B specimens. The respective sensitivity and false-negativity values of CK7/20 staining for Barrett pattern in Group A were 10% and 90%, respectively. These values for gastric pattern in Group B were 40% and 60%, respectively. The specificity and false-positivity values of both patterns were same (100% and 0%, respectively. There was no statistically significant difference for Barrett pattern between the two groups (P = 0.487, while the observation of gastric pattern was significantly higher in Group B than in Group A (P = 0.02. Conclusions We concluded that these

Chemical Control of Black Flies in Large Rivers as an Impact in Agrochemical Residue-Biota Interactions in Water Ecosystems

International Nuclear Information System (INIS)

Haufe, W.O.

1981-01-01

Livestock losses have been an obstacle to economic development of the farming and livestock industry in more northerly areas of Canada until two species of black fly, Simulium arcticum and S. luggeri, outbreaks are controlled effectively. The problem is complicated by its association with an abundance of large rivers and streams. Since effective control of black flies is presently limited to reduction of their breeding sources in flowing water, the managers of Canadian inland waters have been concerned about any major practice of using pesticides as black fly larvicides. Consequently, Canadian inland waters have been subject to continuous monitoring of major drainage systems with special attention to the chlorinated hydrocarbon insecticides. The latest status of residues was published from a Canadian Survey of 333 sampling locations between 1972 and 1975

Protozoan Predation of Escherichia coli O157:H7 Is Unaffected by the Carriage of Shiga Toxin-Encoding Bacteriophages.

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Carrie E Schmidt

Full Text Available Escherichia coli O157:H7 is a food-borne bacterium that causes hemorrhagic diarrhea and hemolytic uremic syndrome in humans. While cattle are a known source of E. coli O157:H7 exposure resulting in human infection, environmental reservoirs may also be important sources of infection for both cattle and humans. Bacteriophage-encoded Shiga toxins (Stx carried by E. coli O157:H7 may provide a selective advantage for survival of these bacteria in the environment, possibly through their toxic effects on grazing protozoa. To determine Stx effects on protozoan grazing, we co-cultured Paramecium caudatum, a common ciliate protozoon in cattle water sources, with multiple strains of Shiga-toxigenic E. coli O157:H7 and non-Shiga toxigenic cattle commensal E. coli. Over three days at ambient laboratory temperature, P. caudatum consistently reduced both E. coli O157:H7 and non-Shiga toxigenic E. coli populations by 1-3 log cfu. Furthermore, a wild-type strain of Shiga-toxigenic E. coli O157:H7 (EDL933 and isogenic mutants lacking the A subunit of Stx 2a, the entire Stx 2a-encoding bacteriophage, and/or the entire Stx 1-encoding bacteriophage were grazed with similar efficacy by both P. caudatum and Tetrahymena pyriformis (another ciliate protozoon. Therefore, our data provided no evidence of a protective effect of either Stx or the products of other bacteriophage genes on protozoan predation of E. coli. Further research is necessary to determine if the grazing activity of naturally-occurring protozoa in cattle water troughs can serve to decrease cattle exposure to E. coli O157:H7 and other Shiga-toxigenic E. coli.

Transcription of human 7S K DNA in vitro and in vivo is exclusively controlled by an upstream promoter

Energy Technology Data Exchange (ETDEWEB)

Kleinert, H.; Benecke, B.J.

1988-02-25

The authors have analyzed the transcription of a recently isolated human 7S K RNA gene in vitro and in vivo. In contrast to hitherto characterized class III genes (genes transcribed by RNA polymerase III), the coding sequence of this gene is not required for faithful and efficient transcription by RNA polymerase III. In fact, a procaryotic vector DNA sequence was efficiently transcribed by RNA polymerase III under the control of the 7S K RNA gene upstream sequence in vitro and in vivo. S/sub 1/-nuclease protection analyses confirmed that the 7S K 5'flanking sequence was sufficient for accurate transcription initiation. These data demonstrate that 7S K DNA represents a novel class III gene, the promoter elements of which are located outside the coding sequence.

Sirtuin7 is involved in protecting neurons against oxygen-glucose deprivation and reoxygenation-induced injury through regulation of the p53 signaling pathway.

Science.gov (United States)

Lv, Jianrui; Tian, Junbin; Zheng, Guoxi; Zhao, Jing

2017-10-01

Sirtuin7 (SIRT7) is known to regulate apoptosis and stress responses. So far, very little is known about the role of SIRT7 in cerebral ischemia/reperfusion injury. In this study, we aimed to investigate the potential role of SIRT7 in regulating oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in neurons. We found a significant increase of SIRT7 expression in neurons in response to OGD/R treatment. Knockdown of SIRT7 aggravated OGD/R-induced injury. Knockdown of SIRT7 augmented the levels of total and acetylated p53 protein. Moreover, knockdown of SIRT7 markedly increased the transcriptional activity of p53 toward apoptosis and activated the p53-mediated proapoptotic signaling pathway. By contrast, overexpression of SIRT7 showed the opposite effects. Taken together, the results of our study suggest that SIRT7 is involved in protecting neurons against OGD/R-induced injury, possibly through regulation of the p53-mediated proapoptotic signaling pathway, indicating a potential therapeutic target for cerebral ischemia/reperfusion injury. © 2017 Wiley Periodicals, Inc.

USP7 Is a Tumor-Specific WNT Activator for APC-Mutated Colorectal Cancer by Mediating β-Catenin Deubiquitination.

Science.gov (United States)

Novellasdemunt, Laura; Foglizzo, Valentina; Cuadrado, Laura; Antas, Pedro; Kucharska, Anna; Encheva, Vesela; Snijders, Ambrosius P; Li, Vivian S W

2017-10-17

The tumor suppressor gene adenomatous polyposis coli (APC) is mutated in most colorectal cancers (CRCs), resulting in constitutive Wnt activation. To understand the Wnt-activating mechanism of the APC mutation, we applied CRISPR/Cas9 technology to engineer various APC-truncated isogenic lines. We find that the β-catenin inhibitory domain (CID) in APC represents the threshold for pathological levels of Wnt activation and tumor transformation. Mechanistically, CID-deleted APC truncation promotes β-catenin deubiquitination through reverse binding of β-TrCP and USP7 to the destruction complex. USP7 depletion in APC-mutated CRC inhibits Wnt activation by restoring β-catenin ubiquitination, drives differentiation, and suppresses xenograft tumor growth. Finally, the Wnt-activating role of USP7 is specific to APC mutations; thus, it can be used as a tumor-specific therapeutic target for most CRCs. Copyright © 2017 The Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention.

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Shanqing Zheng

Full Text Available DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal pathway (IIS, and this is notably true when Caenorhabditis elegans (C. elegans is used to study the action of anti-aging compounds on IIS activity. However, some of these genes may not be specific to DAF-16, even if their expression levels are altered when DAF-16 is activated. Celecoxib was reported to extend the lifespan of C. elegans through activation of DAF-16. Our results confirmed the function of celecoxib on aging; however, we found that the expression of ins-7, a DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an important role in regulating aging, and its expression is suppressed in C. elegans when DAF-16 is activated. However, we found that celecoxib upregulated the expression of ins-7 in contrast to its role in DAF-16 activation. Our subsequent analysis indicated that the expression level of ins-7 in C. elegans was negatively regulated by DAF-16 activity. Additionally, its expression was also positively regulated by DAF-16-independent mechanisms, at least following external pharmacological intervention. Our study suggests that ins-7 is not a specific target gene of DAF-16, and should not be chosen as a reporter for IIS activity. This conclusion is important in the study of INSs on aging in C. elegans, especially under the circumstance of drug intervention.

ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention.

Science.gov (United States)

Zheng, Shanqing; Liao, Sentai; Zou, Yuxiao; Qu, Zhi; Liu, Fan

2014-01-01

DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal pathway (IIS), and this is notably true when Caenorhabditis elegans (C. elegans) is used to study the action of anti-aging compounds on IIS activity. However, some of these genes may not be specific to DAF-16, even if their expression levels are altered when DAF-16 is activated. Celecoxib was reported to extend the lifespan of C. elegans through activation of DAF-16. Our results confirmed the function of celecoxib on aging; however, we found that the expression of ins-7, a DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an important role in regulating aging, and its expression is suppressed in C. elegans when DAF-16 is activated. However, we found that celecoxib upregulated the expression of ins-7 in contrast to its role in DAF-16 activation. Our subsequent analysis indicated that the expression level of ins-7 in C. elegans was negatively regulated by DAF-16 activity. Additionally, its expression was also positively regulated by DAF-16-independent mechanisms, at least following external pharmacological intervention. Our study suggests that ins-7 is not a specific target gene of DAF-16, and should not be chosen as a reporter for IIS activity. This conclusion is important in the study of INSs on aging in C. elegans, especially under the circumstance of drug intervention.

Synaptotagmin-7 is a principal Ca2+ sensor for Ca2+ -induced glucagon exocytosis in pancreas

DEFF Research Database (Denmark)

Gustavsson, Natalia; Wei, Shun-Hui; Hoang, Dong Nhut

2009-01-01

Hormones such as glucagon are secreted by Ca(2+)-induced exocytosis of large dense-core vesicles, but the mechanisms involved have only been partially elucidated. Studies of pancreatic beta-cells secreting insulin revealed that synaptotagmin-7 alone is not sufficient to mediate Ca(2+)-dependent i...

High tunnels: protection for rather than from insect pests?

Science.gov (United States)

Ingwell, Laura L; Thompson, Sarah L; Kaplan, Ian; Foster, Ricky E

2017-12-01

High tunnels are a season extension tool creating a hybrid of field and greenhouse growing conditions. High tunnels have recently increased in the USA and thus research on their management is lacking. One purported advantage of these structures is protection from common field pests, but evidence to support this claim is lacking. We compared insect pest populations in high tunnels with field production over two years for three crops: tomato, broccoli and cucumber. Greenhouse pests (e.g. aphids, whiteflies) were more prevalent in high tunnels, compared to field plots. Hornworms (tobacco (Manduca sexta L.) and tomato (M. quinquemaculata Haworth)), a common field pest on tomato, were also more abundant in high tunnels, requiring chemical control while field populations were low. The crucifer caterpillar complex (imported cabbageworm (Pieris rapae L.), diamondback moth (Plutella xylostella L.) and cabbage looper (Trichoplusia ni Hübner)) was also more abundant in high tunnels in 2010. Cucumber beetle (striped (Acalymma vittatum F.) and spotted (Diabrotica undecimpunctata Mannerheim)) densities were higher in high tunnels in 2010 and field plots in 2011. The common assumption that high tunnels offer protection from field pests was not supported. Instead, high tunnel growing conditions may facilitate higher pest populations. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Breve nota acerca de simúlidos colombianos

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Leopoldo Briceño Iragorry

1946-08-01

Full Text Available Durante corta permanencia en la ciudad de Cali, Colombia (1.000 mts. Alt. 4 de junio de 1946, tuvimos oportunidad de colectar a orillas del rio Cauca a su paso par la prospera capital del Departamento del Valle, ejemplares de Simúlidos al estado de pupa en las inmediaciones del parque donde la admiración conciudadana ha erigido un busto al escritor Jorge Isaacs Iragorri. Pudimos, no obstante las pocas facilidades de que disponíamos, obtener par cría adultos que facilitaron el estudio completo de los ejemplares en referencia, que permitió clasificarlos como Simulium (E lutzianus.

Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation.

Science.gov (United States)

Hosoi, Yoshio; Uno, Yasuhiro; Murayama, Norie; Fujino, Hideki; Shukuya, Mitsunori; Iwasaki, Kazuhide; Shimizu, Makiko; Utoh, Masahiro; Yamazaki, Hiroshi

2012-12-15

Cynomolgus monkeys are widely used as primate models in preclinical studies. However, some differences are occasionally seen between monkeys and humans in the activities of cytochrome P450 enzymes. R- and S-warfarin are model substrates for stereoselective oxidation in humans. In this current research, the activities of monkey liver microsomes and 14 recombinantly expressed monkey cytochrome P450 enzymes were analyzed with respect to R- and S-warfarin 6- and 7-hydroxylation. Monkey liver microsomes efficiently mediated both R- and S-warfarin 7-hydroxylation, in contrast to human liver microsomes, which preferentially catalyzed S-warfarin 7-hydroxylation. R-Warfarin 7-hydroxylation activities in monkey liver microsomes were not inhibited by α-naphthoflavone or ketoconazole, and were roughly correlated with P450 2C19 levels and flurbiprofen 4-hydroxylation activities in microsomes from 20 monkey livers. In contrast, S-warfarin 7-hydroxylation activities were not correlated with the four marker drug oxidation activities used. Among the 14 recombinantly expressed monkey P450 enzymes tested, P450 2C19 had the highest activities for R- and S-warfarin 7-hydroxylations. Monkey P450 3A4 and 3A5 slowly mediated R- and S-warfarin 6-hydroxylations. Kinetic analysis revealed that monkey P450 2C19 had high V(max) and low K(m) values for R-warfarin 7-hydroxylation, comparable to those for monkey liver microsomes. Monkey P450 2C19 also mediated S-warfarin 7-hydroxylation with V(max) and V(max)/K(m) values comparable to those for recombinant human P450 2C9. R-warfarin could dock favorably into monkey P450 2C19 modeled. These results collectively suggest high activities for monkey liver P450 2C19 toward R- and S-warfarin 6- and 7-hydroxylation in contrast to the saturation kinetics of human P450 2C9-mediated S-warfarin 7-hydroxylation. Copyright © 2012 Elsevier Inc. All rights reserved.

Vision screening in children: Is 7-9 years of age a threshold for visual impairment?

Science.gov (United States)

Ertekin, Yusuf Haydar; Tekin, Murat; Uludag, Aysegul; Arikan, Sedat; Sahin, Erkan Melih

2016-01-01

The present study aimed to assess the prevalence of decreased visual acuity, strabismus, and spectacle wear in children aged 5 to 13 years. A cross-sectional study was performed in primary education schools. A total of 1938 participants, including 940 females (48.5%) and 998 males (51.5%) with a mean age 8.96 ± 2.31 (5-13 years old), were screened. The comparisons were performed with gender, age, and age groups. The children attended to vision screening were assigned to three age groups as 5-6 years, 7-9 years, and 10-13 years. The prevalence of the parameters was detected as decreased visual acuity 12.4%, strabismus 2.2%, and spectacle wear 6.9%. The prevalence of decreased visual acuity was significantly higher in girls and in children aged 7-9 years old (p = 0.013, p children aged 7-9 years old (p = 0.019, p visual acuity decrease in 33 of 106 (31.1%) children despite wearing own spectacle. There was no significant difference among three age groups for strabismus. Increased prevalence of decreased visual acuity, as well as the higher frequency of spectacle wear in children at ages of 7-9 years old may point out a threshold for visual impairment.

The intermuscular 3–7 Hz drive is not affected by distal proprioceptive input in myoclonus-dystonia

NARCIS (Netherlands)

Van der Meer, J.N.; Schouten, A.C.; Bour, L.J.; De Vlugt, E.; Van Rootselaar, A.F.; Van der Helm, F.C.T.; Tijssen, M.A.J.

2010-01-01

In dystonia, both sensory malfunctioning and an abnormal intermuscular low-frequency drive of 3–7 Hz have been found, although cause and eVect are unknown. It is hypothesized that sensory processing is primarily disturbed and induces this drive. Accordingly, experimenter-controlled sensory input

Petunia hybrida CAROTENOID CLEAVAGE DIOXYGENASE7 is involved in the production of negative and positive branching signals in petunia.

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Drummond, Revel S M; Martínez-Sánchez, N Marcela; Janssen, Bart J; Templeton, Kerry R; Simons, Joanne L; Quinn, Brian D; Karunairetnam, Sakuntala; Snowden, Kimberley C

2009-12-01

One of the key factors that defines plant form is the regulation of when and where branches develop. The diversity of form observed in nature results, in part, from variation in the regulation of branching between species. Two CAROTENOID CLEAVAGE DIOXYGENASE (CCD) genes, CCD7 and CCD8, are required for the production of a branch-suppressing plant hormone. Here, we report that the decreased apical dominance3 (dad3) mutant of petunia (Petunia hybrida) results from the mutation of the PhCCD7 gene and has a less severe branching phenotype than mutation of PhCCD8 (dad1). An analysis of the expression of this gene in wild-type, mutant, and grafted petunia suggests that in petunia, CCD7 and CCD8 are coordinately regulated. In contrast to observations in Arabidopsis (Arabidopsis thaliana), ccd7ccd8 double mutants in petunia show an additive phenotype. An analysis using dad3 or dad1 mutant scions grafted to wild-type rootstocks showed that when these plants produce adventitious mutant roots, branching is increased above that seen in plants where the mutant roots are removed. The results presented here indicate that mutation of either CCD7 or CCD8 in petunia results in both the loss of an inhibitor of branching and an increase in a promoter of branching.

Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

International Nuclear Information System (INIS)

Sanlioglu, Ahter D; Dirice, Ercument; Aydin, Cigdem; Erin, Nuray; Koksoy, Sadi; Sanlioglu, Salih

2005-01-01

Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4

6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor

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Igor E. Kasheverov

2015-03-01

Full Text Available 6-Bromohypaphorine (6-BHP has been isolated from the marine sponges Pachymatisma johnstoni, Aplysina sp., and the tunicate Aplidium conicum, but data on its biological activity were not available. For the nudibranch mollusk Hermissenda crassicornis no endogenous compounds were known, and here we describe the isolation of 6-BHP from this mollusk and its effects on different nicotinic acetylcholine receptors (nAChR. Two-electrode voltage-clamp experiments on the chimeric α7 nAChR (built of chicken α7 ligand-binding and glycine receptor transmembrane domains or on rat α4β2 nAChR expressed in Xenopus oocytes revealed no action of 6-BHP. However, in radioligand analysis, 6-BHP competed with radioiodinated α-bungarotoxin for binding to human α7 nAChR expressed in GH4C1 cells (IC50 23 ± 1 μM, but showed no competition on muscle-type nAChR from Torpedo californica. In Ca2+-imaging experiments on the human α7 nAChR expressed in the Neuro2a cells, 6-BHP in the presence of PNU120596 behaved as an agonist (EC50 ~80 μM. To the best of our knowledge, 6-BHP is the first low-molecular weight compound from marine source which is an agonist of the nAChR subtype. This may have physiological importance because H. crassicornis, with its simple and tractable nervous system, is a convenient model system for studying the learning and memory processes.

39 CFR 7.7 - Enforcement.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Enforcement. 7.7 Section 7.7 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE PUBLIC OBSERVATION (ARTICLE VII) § 7.7 Enforcement. (a) Under 5 U.S.C. 552b(g), any person may bring a proceeding in the United States...

Nuclear import of high risk HPV16 E7 oncoprotein is mediated by its zinc-binding domain via hydrophobic interactions with Nup62

Energy Technology Data Exchange (ETDEWEB)

Eberhard, Jeremy; Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

2013-11-15

We previously discovered that nuclear import of high risk HPV16 E7 is mediated by a cNLS located within the zinc-binding domain via a pathway that is independent of karyopherins/importins (Angeline et al., 2003; Knapp et al., 2009). In this study we continued our characterization of the cNLS and nuclear import pathway of HPV16 E7. We find that an intact zinc-binding domain is essential for the cNLS function in mediating nuclear import of HPV16 E7. Mutagenesis of cysteine residues to alanine in each of the two CysXXCys motifs involved in zinc-binding changes the nuclear localization of the EGFP-16E7 and 2xEGFP-16E7 mutants. We further discover that a patch of hydrophobic residues, {sub 65}LRLCV{sub 69}, within the zinc-binding domain of HPV16 E7 mediates its nuclear import via hydrophobic interactions with the FG domain of the central channel nucleoporin Nup62. - Highlights: • An intact zinc-binding domain is essential for the nuclear localization of HPV16 E7. • Identification of a hydrophobic patch that is critical for the nuclear import of HPV16 E7. • HPV16 E7 interacts via its zinc-binding domain with the FG domain of Nup62.

The 7-azanorbornane nucleus of epibatidine: 7-azabicyclo[2.2.1]heptan-7-ium chloride

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Sergey N. Britvin

2017-09-01

Full Text Available 7-Azabicyclo[2.2.1]heptane (7-azanorbornane is a bridged heterocyclic nucleus found in epibatidine, the alkaloid isolated from the skin of the tropical poison frog Epipedobates tricolor. Since epibatidine is known as one of the most potent acetylcholine nicotinic receptor agonists, a plethora of literature has been devoted to this alkaloid. However, there are no structural data on the unsubstituted 7-azanorbornane, the parent bicyclic ring of epibatidine and its derivatives. We herein present the structural characterization of the 7-azabicyclo[2.2.1]heptane parent ring as its hydrochloride salt, namely 7-azabicyclo[2.2.1]heptan-7-ium chloride, C6H12N+·Cl−. The compete cation is generated by a crystallographic mirror plane with the N atom lying on the mirror, as does the chloride anion. In the crystal, the cations are linked to the anions by N—H...Cl hydrogen bonds, which generate [001] chains.

Mol 7C/6; Mol 7C/6

Energy Technology Data Exchange (ETDEWEB)

Aberle, J.; Schleisiek, K.; Schmuck, I.; Schmidt, L.; Romer, O.; Weih, G.

1995-08-01

The Mol 7C/6 coolant blockage experiment in the Belgian BR2 reactor yielded results different from Mol 7C experiments with low burnup pins: At 10% burnup local failure is not self-limiting, but requires active systems for detection and scram. The Mol 7C series was finished in 1991. In each of the test bundles Mol 7C/4, /5 and /6, 30 Mk I pins pre-irradiated in KNK II were used. The central blockage consisted of enriched UO{sub 2} covering 30 percent of the bundle cross-section, with a height of 40 mm. The most important system for timely detection of coolant blockages of the type studied in Mol 7C/6 is based on DND. (orig.)

Lichen planus remission is associated with a decrease of human herpes virus type 7 protein expression in plasmacytoid dendritic cells

NARCIS (Netherlands)

de Vries, Henry J. C.; Teunissen, Marcel B. M.; Zorgdrager, Fokla; Picavet, Daisy; Cornelissen, Marion

2007-01-01

The cause of lichen planus is still unknown. Previously we showed human herpes virus 7 (HHV-7) DNA and proteins in lesional lichen planus skin, and significantly less in non-lesional lichen planus, psoriasis or healthy skin. Remarkably, lesional lichen planus skin was infiltrated with plasmacytoid

Recombinant Trichoderma harzianum endoglucanase I (Cel7B) is a highly acidic and promiscuous carbohydrate-active enzyme.

Science.gov (United States)

Pellegrini, Vanessa O A; Serpa, Viviane Isabel; Godoy, Andre S; Camilo, Cesar M; Bernardes, Amanda; Rezende, Camila A; Junior, Nei Pereira; Franco Cairo, João Paulo L; Squina, Fabio M; Polikarpov, Igor

2015-11-01

Trichoderma filamentous fungi have been investigated due to their ability to secrete cellulases which find various biotechnological applications such as biomass hydrolysis and cellulosic ethanol production. Previous studies demonstrated that Trichoderma harzianum IOC-3844 has a high degree of cellulolytic activity and potential for biomass hydrolysis. However, enzymatic, biochemical, and structural studies of cellulases from T. harzianum are scarce. This work reports biochemical characterization of the recombinant endoglucanase I from T. harzianum, ThCel7B, and its catalytic core domain. The constructs display optimum activity at 55 °C and a surprisingly acidic pH optimum of 3.0. The full-length enzyme is able to hydrolyze a variety of substrates, with high specific activity: 75 U/mg for β-glucan, 46 U/mg toward xyloglucan, 39 U/mg for lichenan, 26 U/mg for carboxymethyl cellulose, 18 U/mg for 4-nitrophenyl β-D-cellobioside, 16 U/mg for rye arabinoxylan, and 12 U/mg toward xylan. The enzyme also hydrolyzed filter paper, phosphoric acid swollen cellulose, Sigmacell 20, Avicel PH-101, and cellulose, albeit with lower efficiency. The ThCel7B catalytic domain displays similar substrate diversity. Fluorescence-based thermal shift assays showed that thermal stability is highest at pH 5.0. We determined kinetic parameters and analyzed a pattern of oligosaccharide substrates hydrolysis, revealing cellobiose as a final product of C6 degradation. Finally, we visualized effects of ThCel7B on oat spelt using scanning electron microscopy, demonstrating the morphological changes of the substrate during the hydrolysis. The acidic behavior of ThCel7B and its considerable thermostability hold a promise of its industrial applications and other biotechnological uses under extremely acidic conditions.

41 CFR 302-7.201 - Is temporary storage in excess of authorized limits and excess valuation of goods and services...

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false Is temporary storage in excess of authorized limits and excess valuation of goods and services payable at Government expense? 302-7.201 Section 302-7.201 Public Contracts and Property Management Federal Travel Regulation System...

Pigment pattern in jaguar/obelix zebrafish is caused by a Kir7.1 mutation: implications for the regulation of melanosome movement.

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Motoko Iwashita

2006-11-01

Full Text Available Many animals have a variety of pigment patterns, even within a species, and these patterns may be one of the driving forces of speciation. Recent molecular genetic studies on zebrafish have revealed that interaction among pigment cells plays a key role in pattern formation, but the mechanism of pattern formation is unclear. The zebrafish jaguar/obelix mutant has broader stripes than wild-type fish. In this mutant, the development of pigment cells is normal but their distribution is altered, making these fish ideal for studying the process of pigment pattern formation. Here, we utilized a positional cloning method to determine that the inwardly rectifying potassium channel 7.1 (Kir7.1 gene is responsible for pigment cell distribution among jaguar/obelix mutant fish. Furthermore, in jaguar/obelix mutant alleles, we identified amino acid changes in the conserved region of Kir7.1, each of which affected K(+ channel activity as demonstrated by patch-clamp experiments. Injection of a bacterial artificial chromosome containing the wild-type Kir7.1 genomic sequence rescued the jaguar/obelix phenotype. From these results, we conclude that mutations in Kir7.1 are responsible for jaguar/obelix. We also determined that the ion channel function defect of melanophores expressing mutant Kir7.1 altered the cellular response to external signals. We discovered that mutant melanophores cannot respond correctly to the melanosome dispersion signal derived from the sympathetic neuron and that melanosome aggregation is constitutively activated. In zebrafish and medaka, it is well known that melanosome aggregation and subsequent melanophore death increase when fish are kept under constant light conditions. These observations indicate that melanophores of jaguar/obelix mutant fish have a defect in the signaling pathway downstream of the alpha2-adrenoceptor. Taken together, our results suggest that the cellular defect of the Kir7.1 mutation is directly responsible for

DRG Voltage-Gated Sodium Channel 1.7 Is Upregulated in Paclitaxel-Induced Neuropathy in Rats and in Humans with Neuropathic Pain.

Science.gov (United States)

Li, Yan; North, Robert Y; Rhines, Laurence D; Tatsui, Claudio Esteves; Rao, Ganesh; Edwards, Denaya D; Cassidy, Ryan M; Harrison, Daniel S; Johansson, Caj A; Zhang, Hongmei; Dougherty, Patrick M

2018-01-31

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect experienced by cancer patients receiving treatment with paclitaxel. The voltage-gated sodium channel 1.7 (Na v 1.7) plays an important role in multiple preclinical models of neuropathic pain and in inherited human pain phenotypes, and its gene expression is increased in dorsal root ganglia (DRGs) of paclitaxel-treated rats. Hence, the potential of change in the expression and function of Na v 1.7 protein in DRGs from male rats with paclitaxel-related CIPN and from male and female humans with cancer-related neuropathic pain was tested here. Double immunofluorescence in CIPN rats showed that Na v 1.7 was upregulated in small DRG neuron somata, especially those also expressing calcitonin gene-related peptide (CGRP), and in central processes of these cells in the superficial spinal dorsal horn. Whole-cell patch-clamp recordings in rat DRG neurons revealed that paclitaxel induced an enhancement of ProTx II (a selective Na v 1.7 channel blocker)-sensitive sodium currents. Bath-applied ProTx II suppressed spontaneous action potentials in DRG neurons occurring in rats with CIPN, while intrathecal injection of ProTx II significantly attenuated behavioral signs of CIPN. Complementarily, DRG neurons isolated from segments where patients had a history of neuropathic pain also showed electrophysiological and immunofluorescence results indicating an increased expression of Na v 1.7 associated with spontaneous activity. Na v 1.7 was also colocalized in human cells expressing transient receptor potential vanilloid 1 and CGRP. Furthermore, ProTx II decreased firing frequency in human DRGs with spontaneous action potentials. This study suggests that Na v 1.7 may provide a potential new target for the treatment of neuropathic pain, including chemotherapy (paclitaxel)-induced neuropathic pain. SIGNIFICANCE STATEMENT This work demonstrates that the expression and function of the voltage-gated sodium channel Na

Prmt7 is dispensable in tissue culture models for adipogenic differentiation [v1; ref status: indexed, http://f1000r.es/2im

Directory of Open Access Journals (Sweden)

Yu-Jie Hu

2013-12-01

Full Text Available Protein arginine methylation is a common posttranslational modification that has been implicated in numerous biological processes including gene expression. The mammalian genome encodes nine protein arginine methyltransferases (Prmts that catalyze monomethylation, asymmetric dimethylation, and symmetric dimethylation on arginine residues. Protein arginine methyltransferase 7 (Prmt7 is categorized as a type II and type III enzyme that produces symmetric dimethylated arginine and monomethylated arginine, respectively. However, the biological role of Prmt7 is not well characterized. We previously showed that Prmt5, a type II Prmt that associates with Brg1-based SWI/SNF chromatin remodeling complex, is required for adipocyte differentiation. Since Prmt7 also associates with Brg1-based SWI/SNF complex and modifies core histones, we hypothesized that Prmt7 might play a role in transcriptional regulation of adipogenesis. In the present study, we determined that the expression of Prmt7 did not change throughout adipogenic differentiation of C3H10T1/2 mesenchymal cells. Knockdown or over-expression of Prmt7 had no effect on lipid accumulation or adipogenic gene expression in differentiating C3H10T1/2 cells or in C/EBPα-reprogrammed NIH3T3 fibroblasts. Based on these results, we conclude that Prmt7, unlike Prmt5, is dispensable for adipogenic differentiation in tissue culture models.

A study of onchocerciasis with severe skin and eye lesions in a hyperendemic zone in the forest of southwestern Cameroon: clinical, parasitologic, and entomologic findings.

Science.gov (United States)

Somo, R M; Enyong, P A; Fobi, G; Dinga, J S; Lafleur, C; Agnamey, P; Ngosso, A; Ngolle, E M

1993-01-01

Prior to the initiation of an onchocerciasis control program based on the mass administration of ivermectin in the rain forest of southwestern Cameroon, a preliminary baseline study of the area was conducted. The results of this study showed that onchocerciasis was hyperendemic in the area. Skin symptoms and signs were observed including pruritus (67.4% of the population examined), onchocerca nodules (51.6%), skin depigmentation (18.5%), and hanging groins (5.7%). Except for pruritus, the prevalence of these symptoms increased with age. Of the eyes examined, 44.9% had microfilariae in the anterior chamber, 33.5% had choroidoretinitis, 28.0% had punctate keratitis, 8.3% had papillary abnormalities, and 3.6% had sclerosing keratitis. Vision in 10.5% of the eyes examined was classified as blind or very poor (visual acuity = 0-0.10), in 15.7% as poor (visual acuity = 0.11-0.39), and in 73.8% as good (visual acuity = 0.4-1.00). Unlike previous reports that have linked serious ocular damage mainly to savanna onchocerciasis, the present study showed that forest onchocerciasis also caused significant ocular pathology, including blindness. Parasitologically, positive skin snips were recorded for 92.7% of the persons examined, with both sexes being equally infected. The parasite load, expressed as the geometric mean number of microfilariae per skin snip, was 53.6, and was much higher in males than in females. The flv vector, Simulium squamosum, had a high infection rate of 7.5% infective females in Bakumba and 6.8% infective females in Ngbandi, the two fly-catching points. The transmission potential was 266 infective larvae per person per month in Bakumba and 189 in Ngbandi.

SPG7 Variant Escapes Phosphorylation-Regulated Processing by AFG3L2, Elevates Mitochondrial ROS, and Is Associated with Multiple Clinical Phenotypes

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Naif A.M. Almontashiri

2014-05-01

Full Text Available Mitochondrial production of reactive oxygen species (ROS affects many processes in health and disease. SPG7 assembles with AFG3L2 into the mAAA protease at the inner membrane of mitochondria, degrades damaged proteins, and regulates the synthesis of mitochondrial ribosomes. SPG7 is cleaved and activated by AFG3L2 upon assembly. A variant in SPG7 that replaces arginine 688 with glutamine (Q688 is associated with several phenotypes, including toxicity of chemotherapeutic agents, type 2 diabetes mellitus, and (as reported here coronary artery disease. We demonstrate that SPG7 processing is regulated by tyrosine phosphorylation of AFG3L2. Carriers of Q688 bypass this regulation and constitutively process and activate SPG7 mAAA protease. Cells expressing Q688 produce higher ATP levels and ROS, promoting cell proliferation. Our results thus reveal an unexpected link between the phosphorylation-dependent regulation of the mitochondria mAAA protease affecting ROS production and several clinical phenotypes.

The Vici Syndrome Protein EPG5 Is a Rab7 Effector that Determines the Fusion Specificity of Autophagosomes with Late Endosomes/Lysosomes.

Science.gov (United States)

Wang, Zheng; Miao, Guangyan; Xue, Xue; Guo, Xiangyang; Yuan, Chongzhen; Wang, Zhaoyu; Zhang, Gangming; Chen, Yingyu; Feng, Du; Hu, Junjie; Zhang, Hong

2016-09-01

Mutations in the human autophagy gene EPG5 cause the multisystem disorder Vici syndrome. Here we demonstrated that EPG5 is a Rab7 effector that determines the fusion specificity of autophagosomes with late endosomes/lysosomes. EPG5 is recruited to late endosomes/lysosomes by direct interaction with Rab7 and the late endosomal/lysosomal R-SNARE VAMP7/8. EPG5 also binds to LC3/LGG-1 (mammalian and C. elegans Atg8 homolog, respectively) and to assembled STX17-SNAP29 Qabc SNARE complexes on autophagosomes. EPG5 stabilizes and facilitates the assembly of STX17-SNAP29-VAMP7/8 trans-SNARE complexes, and promotes STX17-SNAP29-VAMP7-mediated fusion of reconstituted proteoliposomes. Loss of EPG5 activity causes abnormal fusion of autophagosomes with various endocytic vesicles, in part due to elevated assembly of STX17-SNAP25-VAMP8 complexes. SNAP25 knockdown partially suppresses the autophagy defect caused by EPG5 depletion. Our study reveals that EPG5 is a Rab7 effector involved in autophagosome maturation, providing insight into the molecular mechanism underlying Vici syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

Electrocortical Activity at 7 Days of Life is Affected in Extremely Premature Infants with Patent Ductus Arteriosus.

Science.gov (United States)

Bruns, N; Metze, B; Bührer, C; Felderhoff-Müser, U; Hüseman, D

2015-09-01

The aim of this study was to determine whether the aEEG at 7 days of life is influenced by the presence of a PDA in non-sedated extremely low gestational age preterm infants. We prospectively recruited infants born at less than 28 weeks of gestation between 11/2007 and 12/2009. aEEGs were recorded at seven days of life and assessed by using the Burdjalov score and the electronically assessed lower border (eLBA). Kruskal-Wallis-Test and linear regression analysis were performed to determine how GA and a PDA affect the aEEG score and the eLBA. Using linear regression analysis we tested which components of the score are affected by a PDA. We recruited 44 infants with a GA of 26.5/7 (23.4/7-27.6/7) weeks and a birth weight of 837 (461-1230) g. The total sum of score points increased from 4 (1-6) to 8 (5-9) points in infants born at 23/24 weeks and 27 weeks of gestation, respectively. In infants with relevant PDA the aEEG scored lower with 8 (3-10) points compared to those with PDA: 5 (1-8) points. Linear regression analysis showed a positive influence of GA and a negative influence of a PDA on the total score. GA had a positive influence on SWC and the visually assessed LBA. A PDA had a negative influence on continuity. The eLBA increased from 4.61 (3.18-5.53) µV to 5.27 (3.38-6.51) µV in infants of 23/24 vs. 27 gestational weeks, but was not significantly influenced by a PDA. A PDA has a negative influence on the total Burdjalov score and continuity at 7 days of age in infants born at less than 28 weeks of gestation. The electrocortical disturbances may be the consequence of a diminished cerebral perfusion in the presence of a PDA. © Georg Thieme Verlag KG Stuttgart · New York.

7 CFR 7.1 - Administration.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Administration. 7.1 Section 7.1 Agriculture Office of the Secretary of Agriculture SELECTION AND FUNCTIONS OF AGRICULTURAL STABILIZATION AND CONSERVATION STATE, COUNTY AND COMMUNITY COMMITTEES § 7.1 Administration. (a) The regulations of this part are...

7 CFR 1221.7 - Customs.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Customs. 1221.7 Section 1221.7 Agriculture... INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.7 Customs. Customs means the U.S. Customs and Border Protection of the U.S. Department of Homeland Security. ...

30 CFR 7.7 - Quality assurance.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Quality assurance. 7.7 Section 7.7 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY General § 7.7 Quality assurance. Applicants granted...

H7N9 Avian Influenza Virus Is Efficiently Transmissible and Induces an Antibody Response in Chickens

Directory of Open Access Journals (Sweden)

Peirong Jiao

2018-04-01

Full Text Available H7N9 viruses pose a threat to human health and they are no less harmful to the poultry industry than the H5N1 avian influenza viruses. However, the pathogenesis, transmissibility, and the host immune response of the H7N9 virus in chickens and mice remain unclear. In this study, we found that H7N9 viruses replicated in multiple organs of the chicken and viral shedding persisted up to 30 days postinoculation (DPI. The viruses were efficiently transmitted between chickens through direct contact. Notably, chickens infected with H7N9 had high antibody levels throughout the entire observation period and their antibody response lasted for 30 DPI. The expression levels of the pattern-recognition receptors and pro-inflammatory cytokines were found to be significantly upregulated in the brain using quantitative real-time PCR. The expression of TLR3, TLR7, MDA5, Mx, IL-1β, IL-6, IFN-α, and IFN-γ were also significantly different in the lungs of infected chickens. We found that the viruses isolated from these birds had low pathogenicity in mice, produced little weight loss and could only replicate in the lungs. Our findings suggested that the H7N9 viruses could replicate in chickens and mice and be efficiently transmitted between chickens, which presented a significant threat to human and poultry health.

7 CFR 502.7 - Gambling.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Gambling. 502.7 Section 502.7 Agriculture Regulations... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.7 Gambling. Participating in games for money or other personal property, or the operation of gambling devices, the conduct...

Inter-domain Synergism Is Required for Efficient Feeding of Cellulose Chain into Active Site of Cellobiohydrolase Cel7A.

Science.gov (United States)

Kont, Riin; Kari, Jeppe; Borch, Kim; Westh, Peter; Väljamäe, Priit

2016-12-09

Structural polysaccharides like cellulose and chitin are abundant and their enzymatic degradation to soluble sugars is an important route in green chemistry. Processive glycoside hydrolases (GHs), like cellobiohydrolase Cel7A of Trichoderma reesei (TrCel7A) are key components of efficient enzyme systems. TrCel7A consists of a catalytic domain (CD) and a smaller carbohydrate-binding module (CBM) connected through the glycosylated linker peptide. A tunnel-shaped active site rests in the CD and contains 10 glucose unit binding sites. The active site of TrCel7A is lined with four Trp residues with two of them, Trp-40 and Trp-38, in the substrate binding sites near the tunnel entrance. Although addressed in numerous studies the elucidation of the role of CBM and active site aromatics has been obscured by a complex multistep mechanism of processive GHs. Here we studied the role of the CBM-linker and Trp-38 of TrCel7A with respect to binding affinity, on- and off-rates, processivity, and synergism with endoglucanase. The CBM-linker increased the on-rate and substrate affinity of the enzyme. The Trp-38 to Ala substitution resulted in increased off-rates and decreased processivity. The effect of the Trp-38 to Ala substitution on on-rates was strongly dependent on the presence of the CBM-linker. This compensation between CBM-linker and Trp-38 indicates synergism between CBM-linker and CD in feeding the cellulose chain into the active site. The inter-domain synergism was pre-requisite for the efficient degradation of cellulose in the presence of endoglucanase. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells

International Nuclear Information System (INIS)

Mishra, Nawneet; Timilsina, Uddhav; Ghimire, Dibya; Dubey, Ravi C.; Gaur, Ritu

2017-01-01

Mitochondrial Dysfunction has been implicated in multiple human diseases, including cancer. Among all cancer, lung cancer is the most common type of cancer worldwide with low survival rates. Mammals possess multiple subunits of the mitochondrial enzyme Cytochrome C oxidase (COX). The COX subunits are expressed in a tissue specific manner and have been implicated in cancer cell metabolism although their molecular and regulatory mechanisms are not clearly understood. In this study, we aimed at identifying novel gene signatures in lung cancer. We performed extensive analysis of seven different Gene Expression Omnibus (GEO) datasets pertaining to different stages of lung adenocarcinoma and identified that multiple subunits of COX genes are differentially expressed in these patients. Amongst all COX genes, the expression of COX7A1 gene was observed to be highly down regulated in these patients. In order to validate the GEO datasets, we looked at the expression of multiple COX genes using quantitative real time PCR (qPCR) using human lung adenocarcinoma cell line A549. Our results confirmed that COX 7A1 gene expression was indeed highly reduced in these cells. Overexpression of COX7A1 in human lung cancer cells led to inhibition of cell proliferation and increase in cell death via apoptosis. These results indicated that low level of COX7A1 gene expression is essential to regulate cell viability and inhibit cell death in lung adenocarcinoma. Our study has identified COX7A1 as a novel gene that might play a crucial role in the etiology of lung adenocarcinoma and can serve as a biomarker for lung cancer disease progression.

Is it necessary to use the entire root as a donor when transferring contralateral C7 nerve to repair median nerve?

Science.gov (United States)

Gao, Kai-Ming; Lao, Jie; Guan, Wen-Jie; Hu, Jing-Jing

2018-01-01

If a partial contralateral C 7 nerve is transferred to a recipient injured nerve, results are not satisfactory. However, if an entire contralateral C 7 nerve is used to repair two nerves, both recipient nerves show good recovery. These findings seem contradictory, as the above two methods use the same donor nerve, only the cutting method of the contralateral C 7 nerve is different. To verify whether this can actually result in different repair effects, we divided rats with right total brachial plexus injury into three groups. In the entire root group, the entire contralateral C 7 root was transected and transferred to the median nerve of the affected limb. In the posterior division group, only the posterior division of the contralateral C 7 root was transected and transferred to the median nerve. In the entire root + posterior division group, the entire contralateral C 7 root was transected but only the posterior division was transferred to the median nerve. After neurectomy, the median nerve was repaired on the affected side in the three groups. At 8, 12, and 16 weeks postoperatively, electrophysiological examination showed that maximum amplitude, latency, muscle tetanic contraction force, and muscle fiber cross-sectional area of the flexor digitorum superficialis muscle were significantly better in the entire root and entire root + posterior division groups than in the posterior division group. No significant difference was found between the entire root and entire root + posterior division groups. Counts of myelinated axons in the median nerve were greater in the entire root group than in the entire root + posterior division group, which were greater than the posterior division group. We conclude that for the same recipient nerve, harvesting of the entire contralateral C 7 root achieved significantly better recovery than partial harvesting, even if only part of the entire root was used for transfer. This result indicates that the entire root should be used as a

Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo

Directory of Open Access Journals (Sweden)

Dustin J. Flanagan

2017-08-01

Full Text Available The gastric epithelium consists of tubular glandular units, each containing several differentiated cell types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. Very little is known about which cell signalling pathways are required for homeostasis of the gastric epithelium. Many diseases, such as cancer, arise as a result of deregulation of signalling pathways that regulate homeostasis of the diseased organ. Therefore, it is important to understand the biology of how normal conditions are maintained in a tissue to help inform the mechanisms driving disease in that same tissue, and to identify potential points of therapeutic intervention. Wnt signalling regulates several cell functions, including proliferation, differentiation and migration, and plays a crucial role during homeostasis of several tissues, including the intestinal epithelium. Wnt3a is required in the culture medium of gastric organoids, suggesting it is also important for the homeostasis of the gastric epithelium, but this has not been investigated in vivo. Here, we show that the Wnt receptor frizzled 7 (Fzd7, which is required for the homeostasis of the intestine, is expressed in the gastric epithelium and is required for gastric organoid growth. Gastric-specific loss of Fzd7 in the adult gastric epithelium of mice is deleterious and triggers rapid epithelial repopulation, which we believe is the first observation of this novel function for this tissue. Taken together, these data provide functional evidence of a crucial role for Wnt signalling, via the Fzd7 receptor, during homeostasis of the gastric epithelium.

7 CFR 503.7 - Gambling.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Gambling. 503.7 Section 503.7 Agriculture Regulations... CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.7 Gambling. Participating in games for money or other personal property, or the operation of gambling devices, the conduct of a lottery or pool, or the selling...

7 CFR 30.7 - Group.

Science.gov (United States)

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Group. 30.7 Section 30.7 Agriculture Regulations of... AND STANDARDS Classification of Leaf Tobacco Covering Classes, Types and Groups of Grades § 30.7 Group. A group of grades, or a division of a type covering several closely related grades, based on the...

2S protein Ara h 7.0201 has unique epitopes compared to other Ara h 7 isoforms and is comparable to 2S proteins Ara h 2 and 6 in basophil degranulation capacity.

Science.gov (United States)

Hayen, S M; Ehlers, A M; den Hartog Jager, C F; Garssen, J; Knol, E F; Knulst, A C; Suer, W; Willemsen, L E M; Otten, H G

2018-07-01

Screening for specific IgE against 2S albumin proteins Ara h 2 and 6 has good positive predictive value in diagnosing peanut allergy. From the third 2S member Ara h 7, 3 isoforms have been identified. Their allergenicity has not been elucidated. This study investigated the allergenicity of Ara h 7 isoforms compared to Ara h 2 and 6. Sensitization of 15 DBPCFC-confirmed peanut-allergic patients to recombinant Ara h 2.0201, Ara h 6.01 and isoforms of recombinant Ara h 7 was determined by IgE immunoblotting strips. A basophil activation test (BAT) was performed in 9 patients to determine IgE-cross-linking capacities of the allergens. Sensitivity to the allergens was tested in 5 patients who were sensitized to at least 1 Ara h 7 isoform, by a concentration range in the BAT. 3D prediction models and sequence alignments were used to visualize differences between isoforms and to predict allergenic epitope regions. Sensitization to Ara h 7.0201 was most frequent (80%) and showed to be equally potent as Ara h 2.0201 and 6.01 in inducing basophil degranulation. Sensitization to Ara h 7.0201 together with Ara h 2.0201 and/or 6.01 was observed, indicating the presence of unique epitopes compared to the other 2 isoforms. Differences between the 3 Ara h 7 isoforms were observed in C-terminal cysteine residues, pepsin and trypsin cleavage sites and 3 single amino acid substitutions. The majority of peanut-allergic patients are sensitized to isoform Ara h 7.0201, which is functionally as active as Ara h 2.0201 and 6.01. Unique epitopes are most likely located in the C-terminus or an allergenic loop region which is a known allergenic epitope region for Ara h 2.0201 and 6.01. Due to its unique epitopes and allergenicity, it is an interesting candidate to improve the diagnostic accuracy for peanut allergy. © 2018 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

OPNET simulation Signaling System No.7 (SS7) network interfaces

OpenAIRE

Ow, Kong Chung.

2000-01-01

This thesis presents an OPNET model and simulation of the Signaling System No.7 (SS7) network, which is dubbed the world's largest data communications network. The main focus of the study is to model one of its levels, the Message Transfer Part Level 3, in accordance with the ITU.T recommendation Q.704. An overview of SS7 that includes the evolution and basics of SS7 architecture is provided to familarize the reader with the topic. This includes the protocol stack, signaling points, signaling...

Low TLR7 gene expression in atherosclerotic plaques is associated with major adverse cardio- and cerebrovascular events

DEFF Research Database (Denmark)

Karadimou, Glykeria; Folkersen, Lasse; Berg, Martin

2016-01-01

Aims: Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome an...

Exercise-induced pyruvate dehydrogenase activation is not affected by 7 days of bed rest

DEFF Research Database (Denmark)

Kiilerich, Kristian; Jørgensen, Stine Ringholm; Biensø, Rasmus Sjørup

2011-01-01

To test the hypothesis that physical inactivity impairs the exercise-induced modulation of pyruvate dehydrogenase (PDH), 6 healthy normally physically active male subjects completed 7 days of bed rest. Before and immediately after the bed rest, the subjects completed an OGTT and a one-legged knee...

Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo.

Science.gov (United States)

Flanagan, Dustin J; Barker, Nick; Nowell, Cameron; Clevers, Hans; Ernst, Matthias; Phesse, Toby J; Vincan, Elizabeth

2017-08-01

The gastric epithelium consists of tubular glandular units, each containing several differentiated cell types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. Very little is known about which cell signalling pathways are required for homeostasis of the gastric epithelium. Many diseases, such as cancer, arise as a result of deregulation of signalling pathways that regulate homeostasis of the diseased organ. Therefore, it is important to understand the biology of how normal conditions are maintained in a tissue to help inform the mechanisms driving disease in that same tissue, and to identify potential points of therapeutic intervention. Wnt signalling regulates several cell functions, including proliferation, differentiation and migration, and plays a crucial role during homeostasis of several tissues, including the intestinal epithelium. Wnt3a is required in the culture medium of gastric organoids, suggesting it is also important for the homeostasis of the gastric epithelium, but this has not been investigated in vivo Here, we show that the Wnt receptor frizzled 7 (Fzd7), which is required for the homeostasis of the intestine, is expressed in the gastric epithelium and is required for gastric organoid growth. Gastric-specific loss of Fzd7 in the adult gastric epithelium of mice is deleterious and triggers rapid epithelial repopulation, which we believe is the first observation of this novel function for this tissue. Taken together, these data provide functional evidence of a crucial role for Wnt signalling, via the Fzd7 receptor, during homeostasis of the gastric epithelium. © 2017. Published by The Company of Biologists Ltd.

7 CFR 1436.7 - Loan term.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Loan term. 1436.7 Section 1436.7 Agriculture... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS FARM STORAGE FACILITY LOAN PROGRAM REGULATIONS § 1436.7 Loan term. (a) For eligible facility loan commodities other than sugar, the term of the loan will be 7...

NONO ubiquitination is mediated by FBW7 and GSK3 β via a degron lost upon chromosomal rearrangement in cancer.

Science.gov (United States)

Alfano, Luigi; Caporaso, Antonella; Altieri, Angela; Costa, Caterina; Forte, Iris M; Iannuzzi, Carmelina A; Barone, Daniela; Esposito, Luca; Giordano, Antonio; Pentimalli, Francesca

2018-05-01

NONO is an RNA-binding protein involved in transcription, mRNA splicing, DNA repair, and checkpoint activation in response to UV radiation. NONO expression has been found altered in several tumor types, including prostate, colon, breast, melanoma, and in papillary renal carcinoma, in which an X chromosome inversion generates a NONO-TFE3 fusion protein. Upon such rearrangement, NONO loses its C-terminal domain. Through bioinformatics analysis, we identified a putative degron motif, known to be recognized by the Skp1-Cul1-F-box-protein (SCF) complex. Here, we evaluated how this domain could affect NONO protein biology. We showed that NONO interacts with the nuclear FBW7α isoform and its ubiquitination is regulated following modulation of the GSK3β kinase. Mutation of T428A/T432A within the degron impaired polyubiquitination upon FBW7α and GSK3β overexpression. Overall, our data suggest that NONO is likely subjected to proteasome-mediated degradation and add NONO to the list of proteins targeted by FBW7, which is itself often deregulated in cancer. © 2017 Wiley Periodicals, Inc.

The Daidzein Metabolite, 6,7,4'-Trihydroxyisoflavone, Is a Novel Inhibitor of PKCα in Suppressing Solar UV-Induced Matrix Metalloproteinase 1

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Tae-Gyu Lim

2014-11-01

Full Text Available Soy isoflavone is an attractive source of functional cosmetic materials with anti-wrinkle, whitening and skin hydration effects. After consumption, the majority of soy isoflavones are converted to their metabolites in the human gastrointestinal tract. To understand the physiological impact of soy isoflavone on the human body, it is necessary to evaluate and address the biological function of its metabolites. In this study, we investigated the effect of 6,7,4'-trihydroxyisoflavone (6,7,4'-THIF, a major metabolite of daidzein, against solar UV (sUV-induced matrix metalloproteinases (MMPs in normal human dermal fibroblasts. MMPs play a critical role in the degradation of collagen in skin, thereby accelerating the aging process of skin. The mitogen-activated protein/extracellular signal-regulated kinase (MEK/extracellular signal-regulated kinase (ERK, mitogen-activated protein kinase (MKK3/6/p38 and MKK4/c-Jun N-terminal kinases (JNK signaling pathways are known to modulate MMP-1 function, and their activation by sUV was significantly reduced by 6,7,4'-THIF pretreatment. Our results also indicated that the enzyme activity of protein kinase C (PKCα, an upstream regulator of MKKs signaling, is suppressed by 6,7,4'-THIF using the in vitro kinase assay. Furthermore, the direct interaction between 6,7,4'-THIF and endogenous PKCα was confirmed using the pull-down assay. Not only sUV-induced MMP-1 expression, but also sUV-induced signaling pathway activation were decreased in PKCα knockdown cells. Overall, we elucidated the inhibitory effect of 6,7,4'-THIF on sUV-induced MMPs and suggest PKCα as its direct molecular target.

Interruption of Onchocerca volvulus transmission in Northern Venezuela

Science.gov (United States)

2013-01-01

Background Onchocerciasis is caused by Onchocerca volvulus and transmitted by Simulium species (black flies). In the Americas, the infection has been previously described in 13 discrete regional foci distributed among six countries (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela) where more than 370,000 people are currently considered at risk. Since 2001, disease control in Venezuela has relied on the mass drug administration to the at-risk communities. This report provides empirical evidence of interruption of Onchocerca volvulus transmission by Simulium metallicum in 510 endemic communities from two Northern foci of Venezuela, after 10–12 years of 6-monthly Mectizan® (ivermectin) treatment to all the eligible residents. Methods In-depth entomologic and epidemiologic surveys were serially conducted from 2001–2012 in selected (sentinel and extra-sentinel) communities from the North-central (NC) and North-east (NE) onchocerciasis foci of Venezuela in order to monitor the impact of ivermectin treatment. Results From 2007–2009, entomological indicators in both foci confirmed that 0 out of 112,637 S. metallicum females examined by PCR contained L3 infection in insect heads. The upper bound of the 95% confidence intervals of the infective rate of the vector reached values below 1% by 2009 (NC) and 2012 (NE). Additionally, after 14 (NC) and 22 (NE) rounds of treatment, the seasonal transmission potential (±UL CIs) of S. metallicum was under the critical threshold of 20 L3 per person per season. Serological analysis in school children < 15 years-old demonstrated that 0 out of 6,590 individuals were harboring antibodies to Ov-16. Finally, epidemiological surveys made during 2010 (NC) and 2012 (NE) showed no evidence of microfilariae in the skin and eyes of the population. Conclusions These results meet the WHO criteria for absence of parasite transmission and disease morbidity in these endemic areas which represent 91% of the population previously at

Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation

International Nuclear Information System (INIS)

Gazzerro, Patrizia; Abbondanza, Ciro; D'Arcangelo, Andrea; Rossi, Mariangela; Medici, Nicola; Moncharmont, Bruno; Puca, Giovanni Alfredo

2006-01-01

The retinoblastoma protein-interacting zinc-finger (RIZ) gene, a member of the nuclear protein methyltransferase superfamily, is characterized by the presence of the N-terminal PR domain. The RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the PR (PRDI-BF1 and RIZ homologous) domain, RIZ2 lacks it. RIZ gene expression is altered in a variety of human cancers and RIZ1 is now considered to be a candidate tumor suppressor. Estradiol treatment of MCF-7 cells produced a selective decrease of RIZ1 transcript and an increase of total RIZ mRNA. Experiments of chromatin immunoprecipitation indicated that RIZ2 protein expression was controlled by estrogen receptor and RIZ1 had a direct repressor function on c-myc gene expression. To investigate the role of RIZ gene products as regulators of the proliferation/differentiation transition, we analyzed the effects of forced suppression of RIZ1 induced in MCF-7 cells by siRNA of the PR domain-containing form. Silencing of RIZ1 expression stimulated cell proliferation, similar to the effect of estradiol on these cells, associated with a transient increase of c-myc expression

Amino Acid Substitutions Improve the Immunogenicity of H7N7HA Protein and Protect Mice against Lethal H7N7 Viral Challenge.

Directory of Open Access Journals (Sweden)

Subaschandrabose Rajesh Kumar

Full Text Available Avian influenza A H7N7/NL/219/03 virus creates a serious pandemic threat to human health because it can transmit directly from domestic poultry to humans and from human to human. Our previous vaccine study reported that mice when immunized intranasally (i.n with live Bac-HA were protected from lethal H7N7/NL/219/03 challenge, whereas incomplete protection was obtained when administered subcutaneously (s.c due to the fact that H7N7 is a poor inducer of neutralizing antibodies. Interestingly, our recent vaccine studies reported that mice when vaccinated subcutaneously with Bac-HA (H7N9 was protected against both H7N9 (A/Sh2/2013 and H7N7 virus challenge. HA1 region of both H7N7 and H7N9 viruses are differ at 15 amino acid positions. Among those, we selected three amino acid positions (T143, T198 and I211 in HA1 region of H7N7. These amino acids are located within or near the receptor binding site. Following the selection, we substituted the amino acid at these three positions with amino acids found on H7N9HA wild-type. In this study, we evaluate the impact of amino acid substitutions in the H7N7 HA-protein on the immunogenicity. We generated six mutant constructs from wild-type influenza H7N7HA cDNA by site directed mutagenesis, and individually expressed mutant HA protein on the surface of baculovirus (Bac-HAm and compared their protective efficacy of the vaccines with Bac-H7N7HA wild-type (Bac-HA by lethal H7N7 viral challenge in a mouse model. We found that mice immunized subcutaneously with Bac-HAm constructs T143A or T198A-I211V or I211V-T143A serum showed significantly higher hemagglutination inhibition and neutralization titer against H7N7 and H7N9 viruses when compared to Bac-HA vaccinated mice groups. We also observed low level of lung viral titer, negligible weight loss and complete protection against lethal H7N7 viral challenge. Our results indicated that amino acid substitution at position 143 or 211 improve immunogenicity of H7N7HA

Nuclear import of cutaneous beta genus HPV8 E7 oncoprotein is mediated by hydrophobic interactions between its zinc-binding domain and FG nucleoporins

Energy Technology Data Exchange (ETDEWEB)

Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

2014-01-20

We have previously discovered and characterized the nuclear import pathways for the E7 oncoproteins of mucosal alpha genus HPVs, type 16 and 11. Here we investigated the nuclear import of cutaneous beta genus HPV8 E7 protein using confocal microscopy after transfections of HeLa cells with EGFP-8E7 and mutant plasmids and nuclear import assays in digitonin-permeabilized HeLa cells. We determined that HPV8 E7 contains a nuclear localization signal (NLS) within its zinc-binding domain that mediates its nuclear import. Furthermore, we discovered that a mostly hydrophobic patch {sub 65}LRLFV{sub 69} within the zinc-binding domain is essential for the nuclear import and localization of HPV8 E7 via hydrophobic interactions with the FG nucleoporins Nup62 and Nup153. Substitution of the hydrophobic residues within the {sub 65}LRLFV{sub 69} patch to alanines, and not R66A mutation, disrupt the interactions between the 8E7 zinc-binding domain and Nup62 and Nup153 and consequently inhibit nuclear import of HPV8 E7. - Highlights: • HPV8 E7 has a cNLS within its zinc-binding domain that mediates its nuclear import. • Discovery of a hydrophobic patch that is critical for the nuclear import of HPV8 E7. • HPV8 E7 nuclear import is mediated by hydrophobic interactions with FG-Nups, Nup62 and Nup153.

The nuclear localization of low risk HPV11 E7 protein mediated by its zinc binding domain is independent of nuclear import receptors

International Nuclear Information System (INIS)

Piccioli, Zachary; McKee, Courtney H.; Leszczynski, Anna; Onder, Zeynep; Hannah, Erin C.; Mamoor, Shahan; Crosby, Lauren; Moroianu, Junona

2010-01-01

We investigated the nuclear import of low risk HPV11 E7 protein using 1) transfection assays in HeLa cells with EGFP fusion plasmids containing 11E7 and its domains and 2) nuclear import assays in digitonin-permeabilized HeLa cells with GST fusion proteins containing 11E7 and its domains. The EGFP-11E7 and EGFP-11cE7 39-98 localized mostly to the nucleus. The GST-11E7 and GST-11cE7 39-98 were imported into the nuclei in the presence of either Ran-GDP or RanG19V-GTP mutant and in the absence of nuclear import receptors. This suggests that 11E7 enters the nucleus via a Ran-dependent pathway, independent of nuclear import receptors, mediated by a nuclear localization signal located in its C-terminal domain (cNLS). This cNLS contains the zinc binding domain consisting of two copies of Cys-X-X-Cys motif. Mutagenesis of Cys residues in these motifs changed the localization of the EGFP-11cE7/-11E7 mutants to cytoplasmic, suggesting that the zinc binding domain is essential for nuclear localization of 11E7.

26 CFR 20.2014-7 - Limitation on credit if a deduction for foreign death taxes is allowed under section 2053(d).

Science.gov (United States)

2010-04-01

... Country X. The Country X tax imposed was at a 50-percent rate on all beneficiaries. A State inheritance... death taxes is allowed under section 2053(d). 20.2014-7 Section 20.2014-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF...

The (7,7) optics at CERN PS

CERN Document Server

Serluca, M; Efthymiopoulos, I; Sperati, F; Sterbini, G; Tecker, F; Zisopoulos, P

2017-01-01

The PS lattice is composed by one hundred combinedfunction magnets, which set the bare tune of the machineto (Qh,Qv) = (6.25, 6.28). Low energy quadrupoles areused at injection to move the tune in a limited working pointarea. In particular the vertical tune is moved below 6.25 toavoid the structural resonance 8Qv= 50 coupled with spacecharge, which leads to strong losses. In view of the highdemands in terms of beam brightness for LIU and HL-LHCprojects, the interest of exploring different integer tune work-ing area started during last years. During 2016, for the firsttime, it has been possible to explore the (7,7) tune workingarea at injection using the auxiliary circuits of the combinedfunction magnets. A finite-element magnetic model, underdevelopment, has been used to predict the required currentsin order to get the desired optical parameters. In this pa-per we present the results and issues encountered duringthe Machine Development (MD) studies about the injectionin the (7,7) area along with optics and be...

New QC 7 tools

International Nuclear Information System (INIS)

1982-03-01

This book tells of new QC with 7 tools which includes TQC and new QC with 7 tools which is for better propel, what is QC method to think? what is new QC 7 tool ? like KJ law, PDPC law, arrow and diagram law, and matrix diagram law, application of new QC 7 tools such as field to apply, application of new QC 7 tools for policy management the method of new QC 7 tools including related regulations KJ law, matrix and data analysis, PDPC law and education and introduction of new QC 7 tools.

Mansonella ozzardi and its vectors in the New World: an update with emphasis on the current situation in Haiti.

Science.gov (United States)

Raccurt, C P

2017-10-25

Mansonella ozzardi (Nematoda: Onchocercidae) is a little studied filarial nematode. This human parasite, transmitted by two families of dipteran vectors, biting midges (most of them members of the genus Culicoides) and blackflies (genus Simulium), is endemic to the Neotropical regions of the New World. With a patchy geographical distribution from southern Mexico to north-western Argentina, human infection with M. ozzardi is highly prevalent in some of the Caribbean islands, along riverine communities in the Amazon Basin, and on both sides of the border between Bolivia and Argentina. Studies conducted in Haiti between 1974 and 1984 allowed the first complete description of the adult worm and permitted clarification of the taxonomic position of this filarial species. This paper reports the known geographical distribution of M. ozzardi in Neotropical regions of the Americas, and focuses on the current situation in Haiti where this filariasis remains a completely neglected public health problem.

7 CFR 295.7 - Indexes.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Indexes. 295.7 Section 295.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE... Officer, Information Technology Division, Food and Nutrition Service, USDA, 3101 Park Center Drive...

7 CFR 1215.7 - Fiscal year.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Fiscal year. 1215.7 Section 1215.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.7...

7 CFR 2903.7 - Project objectives.

Science.gov (United States)

2010-01-01

... AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Program Description § 2903.7 Project objectives. (a) Successful... 7 Agriculture 15 2010-01-01 2010-01-01 false Project objectives. 2903.7 Section 2903.7 Agriculture... following objectives: (1) Enhance current efforts to collect and disseminate biodiesel information; (2...

E7(7) constraints on counterterms in N=8 supergravity

International Nuclear Information System (INIS)

Beisert, N.; Elvang, H.; Freedman, D.; Kiermaier, M.; Morales, A.; Stieberger, S.

2010-01-01

We prove by explicit computation that 6-point matrix elements of D 4 R 4 and D 6 R 4 in N=8 supergravity have non-vanishing single-soft scalar limits, and therefore these operators violate the continuous E 7(7) symmetry. The soft limits precisely match automorphism constraints. Together with previous results for R 4 , this provides a direct proof that no E 7(7) -invariant candidate counterterm exists below 7-loop order. At 7-loops, we characterize the infinite tower of independent supersymmetric operators D 4 R 6 , R 8 , φ 2 R 8 , … with n>4 fields and prove that they all violate E 7(7) symmetry. This means that the 4-graviton amplitude determines whether or not the theory is finite at 7-loop order. We show that the corresponding candidate counterterm D 8 R 4 has a non-linear supersymmetrization such that its single- and double-soft scalar limits are compatible with E 7(7) up to and including 6-points. At loop orders 7,8,9 we provide an exhaustive account of all independent candidate counterterms with up to 16,14,12 fields, respectively, together with their potential single-soft scalar limits.

Induction of Apoptosis by the Severe Acute Respiratory Syndrome Coronavirus 7a Protein Is Dependent on Its Interaction with the Bcl-XL Protein▿

Science.gov (United States)

Tan, Ying-Xim; Tan, Timothy H. P.; Lee, Marvin J.-R.; Tham, Puay-Yoke; Gunalan, Vithiagaran; Druce, Julian; Birch, Chris; Catton, Mike; Fu, Nai Yang; Yu, Victor C.; Tan, Yee-Joo

2007-01-01

The severe acute respiratory syndrome coronavirus (SARS-CoV) 7a protein, which is not expressed by other known coronaviruses, can induce apoptosis in various cell lines. In this study, we show that the overexpression of Bcl-XL, a prosurvival member of the Bcl-2 family, blocks 7a-induced apoptosis, suggesting that the mechanism for apoptosis induction by 7a is at the level of or upstream from the Bcl-2 family. Coimmunoprecipitation experiments showed that 7a interacts with Bcl-XL and other prosurvival proteins (Bcl-2, Bcl-w, Mcl-1, and A1) but not with the proapoptotic proteins (Bax, Bak, Bad, and Bid). A good correlation between the abilities of 7a deletion mutants to induce apoptosis and to interact with Bcl-XL was observed, suggesting that 7a triggers apoptosis by interfering directly with the prosurvival function of Bcl-XL. Interestingly, amino acids 224 and 225 within the C-terminal transmembrane domain of Bcl-XL are essential for the interaction with the 7a protein, although the BH3 domain of Bcl-XL also contributes to this interaction. In addition, fractionation experiments showed that 7a colocalized with Bcl-XL at the endoplasmic reticulum as well as the mitochondria, suggesting that they may form complexes in different membranous compartments. PMID:17428862

HFB7 - A novel orphan hydrophobin of the Harzianum and Virens clades of Trichoderma, is involved in response to biotic and abiotic stresses.

Science.gov (United States)

Przylucka, Agnes; Akcapinar, Gunseli Bayram; Chenthamara, Komal; Cai, Feng; Grujic, Marica; Karpenko, Juriy; Livoi, Miriam; Shen, Qirong; Kubicek, Christian P; Druzhinina, Irina S

2017-05-01

Hydrophobins are small secreted cysteine-rich proteins exclusively found in fungi. They are able to self-assemble in single molecular layers at hydrophobic-hydrophilic interfaces and can therefore be directly involved in establishment of fungi in their habitat. The genomes of filamentous mycotrophic fungi Trichoderma encode a rich diversity of hydrophobins, which are divided in several groups based on their structure and evolution. Here we describe a new member of class II hydrophobins, HFB7, that has a taxonomically restricted occurrence in Harzianum and Virens clades of Trichoderma. Evolutionary analysis reveals that HFB7 proteins form a separate clade distinct from other Trichoderma class II hydrophobins and that genes encoding them evolve under positive selection pressure. Homology modelling of HFB7 structure in comparison to T. reesei HFB2 reveals that the two large hydrophobic patches on the surface of the protein are remarkably conserved between the two hydrophobins despite significant difference in their primary structures. Expression of hfb7 gene in T. virens increases at interactions with other fungi and a plant and in response to a diversity of abiotic stress conditions, and is also upregulated during formation of aerial mycelium in a standing liquid culture. This upregulation significantly exceeds that of expression of hfb7 under a strong constitutive promoter, and T. virens strains overexpressing hfb7 thus display only changes in traits characterized by low hfb7 expression, i.e. faster growth in submerged liquid culture. The hfb7 gene is not expressed in conidia. Our data allow to conclude that this protein is involved in defence of Trichoderma against a diversity of stress factors related to the oxidative stress. Moreover, HFB7 likely helps in the establishment of the fungus in wetlands or other conditions related to high humidity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The balance of TCF7L2 variants with differential activities in Wnt-signaling is regulated by lithium in a GSK3β-independent manner

International Nuclear Information System (INIS)

Struewing, Ian; Boyechko, Tania; Barnett, Corey; Beildeck, Marcy; Byers, Stephen W.; Mao, Catherine D.

2010-01-01

Research highlights: → Identification of a novel effect of lithium on the expression of TCF7L2 RNA isoforms and protein variants. → The extent of lithium-induced TCF7L2 form switch mirrors cell responsiveness to Wnt/β-catenin signaling. → Demonstration that lithium has dual GSK3β-dependent and -independent effects on TCF7L2 expression. → Demonstration that TCF7L2 expression is repressed by the transcriptionally active TCF7L2E form. → Evidence for a lithium-induced de-repression mechanism of TCF7L2 expression via TCF7L2 variant switch. -- Abstract: TCF7L2 transcription factor is a downstream effector of the canonical Wnt/β-catenin signaling, which controls cell fate and homeostasis. However, the complexity of TCF7L2 expression with numerous mRNA isoforms coding for proteins with distinct N- and C-termini allows variability in TCF7L2 functions and regulations. Here, we show that although TCF7L2 mRNA isoforms distinguish fetal, immortalized and adult differentiated endothelial cells (EC), they cannot explain the lack of significant β-catenin/TCF7 activities in ECs. Lithium, a Wnt-signaling activator, increases TCF7L2 mRNA levels and induces an RNA isoform switch favoring the expression of TCF7L2-short forms lacking the C-termini domains. Although the latter occurs in different cell types, its extent depends on the overall increase of TCF7L2 transcription, which correlates with cell responsiveness to Wnt/β-catenin signaling. While GSK3β down-regulation increases TCF7L2 expression, there is no concomitant change in TCF7L2 mRNA isoforms, which demonstrate the dual effects of lithium on TCF7L2 expression via a GSK3β-dependent up-regulation and a GSK3β-independent modulation of RNA splicing. TCF7L2E-long forms display a repressor activity on TCF7L2-promoter reporters and lithium induces a decrease of the endogenous TCF7L2 forms bound to native TCF7L2-promoter chromatin at two novel distal TCF7-binding sites. Altogether our data reveal a lithium

7 CFR 984.7 - Marketing year.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing year. 984.7 Section 984.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 984.7 Marketing year. Marketing year means the twelve months from September...

7 CFR 274.7 - Coupon management.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Coupon management. 274.7 Section 274.7 Agriculture... FOOD STAMP AND FOOD DISTRIBUTION PROGRAM ISSUANCE AND USE OF COUPONS § 274.7 Coupon management. (a) Coupon inventory management. State agencies shall establish coupon inventory management systems which...

7 CFR 983.7 - Certified pistachios.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Certified pistachios. 983.7 Section 983.7 Agriculture... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE PISTACHIOS GROWN IN CALIFORNIA, ARIZONA, AND NEW MEXICO Definitions § 983.7 Certified pistachios. Certified pistachios are those that meet...

7 CFR 1230.7 - Customs Service.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Customs Service. 1230.7 Section 1230.7 Agriculture... CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Definitions § 1230.7 Customs Service. Customs Service means the United States Customs Service of the United States Department of...

7 CFR 371.7 - Animal Care.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Animal Care. 371.7 Section 371.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ORGANIZATION, FUNCTIONS, AND DELEGATIONS OF AUTHORITY § 371.7 Animal Care. (a...

7 CFR 7.17 - Dual office.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Dual office. 7.17 Section 7.17 Agriculture Office of... STATE, COUNTY AND COMMUNITY COMMITTEES § 7.17 Dual office. (a) County committee membership. A member of... any other county office employee. (b) Community committee membership. A member of the community...

7 CFR 277.7 - Cash depositories.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Cash depositories. 277.7 Section 277.7 Agriculture... FOOD STAMP AND FOOD DISTRIBUTION PROGRAM PAYMENTS OF CERTAIN ADMINISTRATIVE COSTS OF STATE AGENCIES § 277.7 Cash depositories. (a) The term “cash depositories” refers to banks or other institutions which...

7 CFR 993.7 - French prunes.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false French prunes. 993.7 Section 993.7 Agriculture... Order Regulating Handling Definitions § 993.7 French prunes. French prunes means: (a) Prunes produced from plums of the following varieties of plums: French (Prune d'Agen, Petite Prune d'Agen), Coates (Cox...

Quality Assurance Tracking System - R7 (QATS-R7)

Data.gov (United States)

U.S. Environmental Protection Agency — This is metadata documentation for the Quality Assurance Tracking System - R7, an EPA Region 7 resource that tracks information on quality assurance reviews. Also...

Synaptotagmin-7 Is an Asynchronous Calcium Sensor for Synaptic Transmission in Neurons Expressing SNAP-23

DEFF Research Database (Denmark)

Weber, Jens P; Toft-Bertelsen, Trine L; Mohrmann, Ralf

2014-01-01

Synchronization of neurotransmitter release with the presynaptic action potential is essential for maintaining fidelity of information transfer in the central nervous system. However, synchronous release is frequently accompanied by an asynchronous release component that builds up during repetitive...... stimulation, and can even play a dominant role in some synapses. Here, we show that substitution of SNAP-23 for SNAP-25 in mouse autaptic glutamatergic hippocampal neurons results in asynchronous release and a higher frequency of spontaneous release events (mEPSCs). Use of neurons from double-knock-out (SNAP......, while synaptotagmin-7 barely displayed activity-dependent trafficking between vesicle and plasma membrane, implying that it acts as a plasma membrane calcium sensor. Overall, these findings support the idea of alternative syt∶SNARE combinations driving release with different kinetics and fidelity....

Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

Energy Technology Data Exchange (ETDEWEB)

Onder, Zeynep; Chang, Vivian; Moroianu, Junona, E-mail: moroianu@bc.edu

2015-01-01

We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), {sub 76}IRTFQELLF{sub 84}, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7.

Implanted $^{7}$Be targets for the study of neutron interactions with $^{7}$Be

CERN Multimedia

The disagreement of the predicted abundance of primordial $^{7}$Li with the observed abundance is a longstanding problem in Big Bang Nucleosynthesis (BBN) theory (“Primordial $^{7}$Li problem”). While BBN theory correctly predicts the relative abundances of $^{2}$H/$^{1}$H, $^{3}$He/$^{1}$H and $^{4}$He/$^{1}$H (that vary over four orders of magnitudes), but it over-predicts the relative abundance of primordial $^{7}$Li/$^{1}$H by a factor of approximately 3-4 larger than observed (approximately 4-5$\\sigma$ discrepancy). Primordial $^{7}$Li is destroyed during the first 15 minutes primarily via the $^{7}$Li(p,$\\alpha$) reaction. Hence most of the primordial $^7$Li is predicted as the result of the (later when atoms are formed) electron capture $\\beta$-decay of the primordial $^{7}$Be that is produced primarily in the $^{3}$He($\\alpha$,$\\gamma$) )$^{7}$Be reaction. We propose to investigate the direct destruction of $^{7}$Be during (the first 15 minutes of) BBN via the $^{7}$Be(n,$\\alpha$) reaction to ch...

An Apoplastic β-Glucosidase is Essential for the Degradation of Flavonol 3-O-β-Glucoside-7-O-α-Rhamnosides in Arabidopsis.

Science.gov (United States)

Roepke, Jonathon; Gordon, Harley O W; Neil, Kevin J A; Gidda, Satinder; Mullen, Robert T; Freixas Coutin, José A; Bray-Stone, Delaney; Bozzo, Gale G

2017-06-01

, BGLU15 is essential for catabolism of flavonol 3-O-β-glucoside-7-O-α-rhamnosides and flavonol 3-O-β-glucosides in Arabidopsis. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

RELAP-7 Theory Manual

Energy Technology Data Exchange (ETDEWEB)

Berry, Ray Alden [Idaho National Lab. (INL), Idaho Falls, ID (United States); Zou, Ling [Idaho National Lab. (INL), Idaho Falls, ID (United States); Zhao, Haihua [Idaho National Lab. (INL), Idaho Falls, ID (United States); Zhang, Hongbin [Idaho National Lab. (INL), Idaho Falls, ID (United States); Peterson, John William [Idaho National Lab. (INL), Idaho Falls, ID (United States); Martineau, Richard Charles [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kadioglu, Samet Yucel [Idaho National Lab. (INL), Idaho Falls, ID (United States); Andrs, David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-03-01

This document summarizes the physical models and mathematical formulations used in the RELAP-7 code. In summary, the MOOSE based RELAP-7 code development is an ongoing effort. The MOOSE framework enables rapid development of the RELAP-7 code. The developmental efforts and results demonstrate that the RELAP-7 project is on a path to success. This theory manual documents the main features implemented into the RELAP-7 code. Because the code is an ongoing development effort, this RELAP-7 Theory Manual will evolve with periodic updates to keep it current with the state of the development, implementation, and model additions/revisions.

Analysis of translesion DNA synthesis activity of the human REV1-REV7 complex, which is a key player in radiation-induced mutagenesis

International Nuclear Information System (INIS)

Masuda, Y.; Masuda, K.; Kamiya, K.

2003-01-01

Full text: Ionizing radiation frequently causes oxidative DNA damage in cells. It has been suggested that functions of the REV1 and REV7 genes are induction of mutations and prevention of cell death caused by ionizing radiation. With yeast Saccharomyces cerevisiae, results from a variety of investigations have demonstrated that the REV genes play a major role in induction of mutations through replication processes which directly copy the damaged DNA template during DNA replication. However, in higher eucaryotes, functions of homologues are poorly understood and appear somewhat different from the yeast case. It has been suggested that human REV1 interacts with human REV7, this being specific to higher eucaryotes. Here we show that purified human REV1 and REV7 proteins form a heterodimer in solution, which is stable through intensive purification steps. Results from biochemical analysis of the transferase reactions of the REV1-REV7 complex demonstrated, in contrast to the case of yeast Rev3 whose polymerase activity is stimulated by assembly with yeast Rev7, that human REV7 did not influence the stability, substrate specificity or kinetic parameters of the transferase reactions of REV1 protein. A possible molecular role of the REV7 subunit may be to help assembly of the REV1 protein to a large complex containing REV3 and/or other DNA polymerases in higher eucaryotes

Figure 7

Data.gov (United States)

U.S. Environmental Protection Agency — Two files provided. The ENS.tar file contains text data files (*.csv) used to create Figure 7 and Figure 8. The Figure7.txt is an R script that reads these files and...

7 CFR 1486.301 - How is the working relationship established between CCC and the Recipient of program funding?

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false How is the working relationship established between... relationship established between CCC and the Recipient of program funding? (a) FAS will send an approval letter... agreement and submit it to the Director, Marketing Operations Staff, FAS, USDA. The applicant may not be...

HOXB7 mRNA is overexpressed in pancreatic ductal adenocarcinomas and its knockdown induces cell cycle arrest and apoptosis

International Nuclear Information System (INIS)

Chile, Thais; Bacchella, Telésforo; Giorgi, Ricardo Rodrigues; Fortes, Maria Angela Henriques Zanella; Corrêa-Giannella, Maria Lúcia Cardillo; Brentani, Helena Paula; Maria, Durvanei Augusto; Puga, Renato David; Paula, Vanessa de Jesus R de; Kubrusly, Marcia Saldanha; Novak, Estela Maria

2013-01-01

Human homeobox genes encode nuclear proteins that act as transcription factors involved in the control of differentiation and proliferation. Currently, the role of these genes in development and tumor progression has been extensively studied. Recently, increased expression of HOXB7 homeobox gene (HOXB7) in pancreatic ductal adenocarcinomas (PDAC) was shown to correlate with an invasive phenotype, lymph node metastasis and worse survival outcomes, but no influence on cell proliferation or viability was detected. In the present study, the effects arising from the knockdown of HOXB7 in PDAC cell lines was investigated. Real time quantitative PCR (qRT-PCR) (Taqman) was employed to assess HOXB7 mRNA expression in 29 PDAC, 6 metastatic tissues, 24 peritumoral tissues and two PDAC cell lines. siRNA was used to knockdown HOXB7 mRNA in the cell lines and its consequences on apoptosis rate and cell proliferation were measured by flow cytometry and MTT assay respectively. Overexpression of HOXB7 mRNA was observed in the tumoral tissues and in the cell lines MIA PaCa-2 and Capan-1. HOXB7 knockdown elicited (1) an increase in the expression of the pro-apoptotic proteins BAX and BAD in both cell lines; (2) a decrease in the expression of the anti-apoptotic protein BCL-2 and in cyclin D1 and an increase in the number of apoptotic cells in the MIA PaCa-2 cell line; (3) accumulation of cell in sub-G1 phase in both cell lines; (4) the modulation of several biological processes, especially in MIA PaCa-2, such as proteasomal ubiquitin-dependent catabolic process and cell cycle. The present study confirms the overexpression of HOXB7 mRNA expression in PDAC and demonstrates that decreasing its protein level by siRNA could significantly increase apoptosis and modulate several biological processes. HOXB7 might be a promising target for future therapies

Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7.

Science.gov (United States)

Leegwater, Peter A; Vos-Loohuis, Manon; Ducro, Bart J; Boegheim, Iris J; van Steenbeek, Frank G; Nijman, Isaac J; Monroe, Glen R; Bastiaansen, John W M; Dibbits, Bert W; van de Goor, Leanne H; Hellinga, Ids; Back, Willem; Schurink, Anouk

2016-10-28

Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease process at the molecular level. We have localized the genetic cause of the dwarfism phenotype by a genome wide approach to a 3 Mb region on the p-arm of equine chromosome 14. The DNA of two dwarfs and one control Friesian horse was sequenced completely and we identified the missense mutation ECA14:g.4535550C > T that cosegregated with the phenotype in all Friesians analyzed. The mutation leads to the amino acid substitution p.(Arg17Lys) of xylosylprotein beta 1,4-galactosyltransferase 7 encoded by B4GALT7. The protein is one of the enzymes that synthesize the tetrasaccharide linker between protein and glycosaminoglycan moieties of proteoglycans of the extracellular matrix. The mutation not only affects a conserved arginine codon but also the last nucleotide of the first exon of the gene and we show that it impedes splicing of the primary transcript in cultured fibroblasts from a heterozygous horse. As a result, the level of B4GALT7 mRNA in fibroblasts from a dwarf is only 2 % compared to normal levels. Mutations in B4GALT7 in humans are associated with Ehlers-Danlos syndrome progeroid type 1 and Larsen of Reunion Island syndrome. Growth retardation and ligamentous laxity are common manifestations of these syndromes. We suggest that the identified mutation of equine B4GALT7 leads to the typical dwarfism phenotype in Friesian horses due to deficient splicing of transcripts of

1RXS J180834.7+101041 is a new cataclysmic variable with non-uniform disc

Science.gov (United States)

Yakin, D. G.; Suleimanov, V. F.; Shimansky, V. V.; Borisov, N. V.; Bikmaev, I. F.; Sakhibullin, N. A.

2010-11-01

Results of photometric and spectroscopic investigations of the recently discovered disc cataclysmic variable star 1RXS J180834.7+101041 are presented. Emission spectra of the system show broad double peaked hydrogen and helium emission lines. Doppler maps for the hydrogen lines demonstrate strongly non-uniform emissivity distribution in the disc, similar to that found in IP Peg. It means that the system is a new cataclysmic variable with a spiral density wave in the disc. Masses of the components (MWD = 0.8+/-0.22 Msolar and MRD = 0.14+/-0.02 Msolar), and the orbit inclination (i = 78°+/- 1.°5) were estimated using the various well-known relations for cataclysmic variables.

Structure and Cancer Immunotherapy of the B7 Family Member B7x

Science.gov (United States)

Jeon, Hyungjun; Vigdorovich, Vladimir; Garrett-Thomson, Sarah C.; Janakiram, Murali; Ramagopal, Udupi A.; Abadi, Yael M.; Lee, Jun Sik; Scandiuzzi, Lisa; Ohaegbulam, Kim C; Chinai, Jordan M; Zhao, Ruihua; Yao, Yu; Mao, Ying; Sparano, Joseph A.; Almo, Steven C.; Zang, Xingxing

2014-01-01

SUMMARY B7x (B7-H4 or B7S1) is a member of the B7 family that can inhibit T cell function. B7x protein is absent in most normal human tissues and immune cells, but is overexpressed in human cancers and often correlates with negative clinical outcome. The expression pattern and function of B7x suggest that it may be a potent immunosuppressive pathway in human cancers. Here we determined the crystal structure of human B7x IgV domain at 1.59Å resolution and mapped the epitopes recognized by monoclonal antibodies. We developed a new in vivo system to screen therapeutic monoclonal antibodies against B7x, and found that the clone 1H3 significantly inhibited growth of B7x-expressing tumor in vivo via multiple mechanisms. Furthermore, the surviving mice given 1H3 treatment were resistant to tumor re-challenge. Our data suggest that targeting B7x on tumors is a promising cancer immunotherapy and humanized 1H3 may be efficacious for immunotherapy of human cancers. PMID:25437562

Structure and Cancer Immunotherapy of the B7 Family Member B7x

Directory of Open Access Journals (Sweden)

Hyungjun Jeon

2014-11-01

Full Text Available B7x (B7-H4 or B7S1 is a member of the B7 family that can inhibit T cell function. B7x protein is absent in most normal human tissues and immune cells, but it is overexpressed in human cancers and often correlates with negative clinical outcome. The expression pattern and function of B7x suggest that it may be a potent immunosuppressive pathway in human cancers. Here, we determined the crystal structure of the human B7x immunoglobulin variable (IgV domain at 1.59 Å resolution and mapped the epitopes recognized by monoclonal antibodies. We developed an in vivo system to screen therapeutic monoclonal antibodies against B7x and found that the clone 1H3 significantly inhibited growth of B7x-expressing tumors in vivo via multiple mechanisms. Furthermore, the surviving mice given 1H3 treatment were resistant to tumor rechallenge. Our data suggest that targeting B7x on tumors is a promising cancer immunotherapy and humanized 1H3 may be efficacious for immunotherapy of human cancers.

Androgen Receptor Variant AR-V9 Is Coexpressed with AR-V7 in Prostate Cancer Metastases and Predicts Abiraterone Resistance.

Science.gov (United States)

Kohli, Manish; Ho, Yeung; Hillman, David W; Van Etten, Jamie L; Henzler, Christine; Yang, Rendong; Sperger, Jamie M; Li, Yingming; Tseng, Elizabeth; Hon, Ting; Clark, Tyson; Tan, Winston; Carlson, Rachel E; Wang, Liguo; Sicotte, Hugues; Thai, Ho; Jimenez, Rafael; Huang, Haojie; Vedell, Peter T; Eckloff, Bruce W; Quevedo, Jorge F; Pitot, Henry C; Costello, Brian A; Jen, Jin; Wieben, Eric D; Silverstein, Kevin A T; Lang, Joshua M; Wang, Liewei; Dehm, Scott M

2017-08-15

Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies. Accordingly, efforts are under way to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC). The purpose of this study was to understand whether other AR variants may be coexpressed with AR-V7 and promote resistance to AR-targeted therapies. Experimental Design: We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models. Coexpression of AR-V7 and AR-V9 mRNA in CRPC metastases and circulating tumor cells was assessed by RNA-seq and RT-PCR, respectively. Expression of AR-V9 protein in CRPC models was evaluated with polyclonal antisera. Multivariate analysis was performed to test whether AR variant mRNA expression in metastatic tissues was associated with a 12-week progression-free survival endpoint in a prospective clinical trial of 78 CRPC-stage patients initiating therapy with the androgen synthesis inhibitor, abiraterone acetate. Results: AR-V9 was frequently coexpressed with AR-V7. Both AR variant species were found to share a common 3' terminal cryptic exon, which rendered AR-V9 susceptible to experimental manipulations that were previously thought to target AR-V7 uniquely. AR-V9 promoted ligand-independent growth of prostate cancer cells. High AR-V9 mRNA expression in CRPC metastases was predictive of primary resistance to abiraterone acetate (HR = 4.0; 95% confidence interval, 1.31-12.2; P = 0.02). Conclusions: AR-V9 may be an important component of therapeutic resistance in CRPC. Clin Cancer Res; 23(16); 4704-15. ©2017 AACR . ©2017 American Association for Cancer Research.

Human-like PB2 627K influenza virus polymerase activity is regulated by importin-α1 and -α7.

Directory of Open Access Journals (Sweden)

Ben Hudjetz

2012-01-01

Full Text Available Influenza A viruses may cross species barriers and transmit to humans with the potential to cause pandemics. Interplay of human- (PB2 627K and avian-like (PB2 627E influenza polymerase complexes with unknown host factors have been postulated to play a key role in interspecies transmission. Here, we have identified human importin-α isoforms (α1 and α7 as positive regulators of human- but not avian-like polymerase activity. Human-like polymerase activity correlated with efficient recruitment of α1 and α7 to viral ribonucleoprotein complexes (vRNPs without affecting subcellular localization. We also observed that human-like influenza virus growth was impaired in α1 and α7 downregulated human lung cells. Mice lacking α7 were less susceptible to human- but not avian-like influenza virus infection. Thus, α1 and α7 are positive regulators of human-like polymerase activity and pathogenicity beyond their role in nuclear transport.

Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway.

Science.gov (United States)

Onder, Zeynep; Chang, Vivian; Moroianu, Junona

2015-01-01

We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP-8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), 76IRTFQELLF84, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. Copyright © 2014 Elsevier Inc. All rights reserved.

Duplication of 7q36.3 encompassing the Sonic Hedgehog (SHH) gene is associated with congenital muscular hypertrophy

DEFF Research Database (Denmark)

Kristensen, Lone Krøldrup; Kjaergaard, S; Kirchhoff, Marianne

2012-01-01

with muscular hypertrophy and mildly retarded psychomotor development. Array-CGH identified a small duplication of 7q36.3 including the Sonic Hedgehog (SHH) gene in both the aborted foetus and the live born male sib. Neither of the parents carried the 7q36.3 duplication. The consequences of overexpression...

Gain of chromosome 7 by chromogenic in situ hybridization (CISH) in chordomas is correlated to c-MET expression.

Science.gov (United States)

Walter, Beatriz A; Begnami, Maria; Valera, Vladimir A; Santi, Mariarita; Rushing, Elisabeth J; Quezado, Martha

2011-01-01

Chordomas are low to intermediate grade malignancies that arise from remnants of embryonic notochord. They often recur after surgery and are highly resistant to conventional adjuvant therapies. Recently, the development of effective targeted molecular therapy has been investigated in chordomas that show receptors for tyrosine kinase (RTKs) activation. Expression of specific RTKs such as Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial transition factor (c-MET) in chordomas may offer valuable therapeutic options. We investigated changes in copy number of chromosome 7 and correlated it with EGFR gene status and EGFR and c-MET protein expression in 22 chordoma samples. Chromosome 7 copy number was evaluated by chromogenic in situ hybridization (CISH) and protein expression of EGFR and c-MET by immunohistochemistry. Tumors mostly showed conventional histopathologic features and were found mainly in sacral (41%) and cranial sites (54.5%). Aneusomy of chromosome 7 was seen in 73% of the samples, 62% of primary tumors and in all recurrent chordomas. EGFR and c-MET were both expressed, but only c-MET protein expression was significantly correlated with chromosome 7 aneusomy (P ≤ 0.001). c-MET overexpression may represent an early chromosome 7 alteration that could play an important role during chordoma pathogenesis. c-MET overexpression shows promise as a molecular marker of response to targeted molecular therapy in the treatment of chordomas.

7 CFR 1209.7 - Fiscal year.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Fiscal year. 1209.7 Section 1209.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209...

“Ni{sub 5}TiO{sub 7}” is Ni{sub 5}TiO{sub 4}(BO{sub 3}){sub 2}

Energy Technology Data Exchange (ETDEWEB)

Nalbandyan, V.B.

2017-05-15

It is shown that the compound known as Ni{sub 5}TiO{sub 7} and considered as a promising catalyst and oxidation product of alloys does not exist and its XRD pattern actually corresponds to Ni{sub 5}TiO{sub 4}(BO{sub 3}){sub 2} - Graphical abstract: XRD pattern of “Ni{sub 5}TiO{sub 7}” (top) is identical to that for Ni{sub 5}TiO{sub 4}(BO{sub 3}){sub 2} (bottom) based on single-crystal structural data. - Highlights: • Popular catalyst known as Ni{sub 5}TiO{sub 7} is actually Ni{sub 5}TiO{sub 4}(BO{sub 3}){sub 2}. • B{sub 2}O{sub 3} came from the flux used for crystal growth. • Some authors reporting this phase did not use any boron compounds.

Adsorption of 1,3-butadiene on Si(111)7x7 surface

International Nuclear Information System (INIS)

An, K.-S.; Kim, Y.; Baik, J.Y.; Park, C.-Y.; Kim, B.

2004-01-01

Full text: The adsorption of 1,3-butadiene (BD : C 4 H 10 ) on the Si(111)7x7 surface has been investigated using synchrotron radiation photoemission spectroscopy and scanning tunneling microscopy. BD adsorbs on the Si(111)7x7 surface at room temperature, not only adatom-rest-atom bridging but also adatom-adatom bridging type. In the valence band spectrum for the Si(111)7x7 surface, the adatom and rest-atom states were observed at the binding energies of about 0.2 and 0.8 eV, respectively. With increasing BD exposure, the adatom state is completely quenched at an initial exposure, while the rest-atom state disappears at higher exposure. This indicates two different reaction pathways of BD on the Si(111)7x7 surface. STM shows three different adsorption types on the 7x7 surface, two adatom-adatom bridging and one adatom-rest-atom bridging types. By comparing the valence band and Si 2p core level spectra with STM images, it was found that the chemical reactivity of BD molecule with the adatom-rest-atom pair is strongly higher than the adatom-adatom pair

Resistive ballooning modes in W7-AS and W7-X

International Nuclear Information System (INIS)

Kaiser, R.

1993-01-01

'Critical' pressure gradients due to resistive ballooning modes and their growth rates were computed for the W7-AS stellarator and for a HELIAS configuration with W7-X parameters, and the two configurations were compared. The results are based on the evaluation of a fourth order magnetic differential equation along closed magnetic field lines. The numerical procedure applying a variational approach uses the 'Garching resistive ballooning code', GARBO, which was originally developed for the stability analysis of axisymmetric plasmas. Concerning purely growing modes, this analysis shows that the favourable stability properties of W7-X, already optimized with respect to ideal ballooning modes, persist in the resistive regime: the destabilizing effect of resistivity is largely compensated by the stabilizing contribution of plasma compression. As a consequence, the ideal β limit continues only moderately shifted in the resistive case and likewise ideal ballooning stable equilibria (up to β 0 ≅ 5%) do not become resistively unstable. The situation is different for W7-AS. Greater resistive effects (in comparison with W7-X) are found in a configuration that is already ideally much more unstable. A basic feature in resistive calculations is the occurrence of overstable modes. These modes no longer show a stability threshold and, for realistic values of pressure and resistivity, linear instability is obtained for W7-AS as well as for W7-X, with growth rates and oscillation frequencies in the kilo-Hertz range. (author). 29 refs, 13 figs

P2X7-Regulated Protection from Exacerbations and Loss of Control Is Independent of Asthma Maintenance Therapy

Science.gov (United States)

Manthei, David M.; Seibold, Max A.; Ahn, Kwangmi; Bleecker, Eugene; Boushey, Homer A.; Calhoun, William J.; Castro, Mario; Chinchili, Vernon M.; Fahy, John V.; Hawkins, Greg A.; Icitovic, Nicolina; Israel, Elliot; Jarjour, Nizar N.; King, Tonya; Kraft, Monica; Lazarus, Stephen C.; Lehman, Erik; Martin, Richard J.; Meyers, Deborah A.; Peters, Stephen P.; Sheerar, Dagna; Shi, Lei; Sutherland, E. Rand; Szefler, Stanley J.; Wechsler, Michael E.; Sorkness, Christine A.; Lemanske, Robert F.

2013-01-01

Rationale: The function of the P2X7 nucleotide receptor protects against exacerbation in people with mild-intermittent asthma during viral illnesses, but the impact of disease severity and maintenance therapy has not been studied. Objectives: To evaluate the association between P2X7, asthma exacerbations, and incomplete symptom control in a more diverse population. Methods: A matched P2RX7 genetic case-control was performed with samples from Asthma Clinical Research Network trial participants enrolled before July 2006, and P2X7 pore activity was determined in whole blood samples as an ancillary study to two trials completed subsequently. Measurements and Main Results: A total of 187 exacerbations were studied in 742 subjects, and the change in asthma symptom burden was studied in an additional 110 subjects during a trial of inhaled corticosteroids (ICS) dose optimization. African American carriers of the minor G allele of the rs2230911 loss-of-function single nucleotide polymorphism were more likely to have a history of prednisone use in the previous 12 months, with adjustment for ICS and long-acting β2-agonists use (odds ratio, 2.7; 95% confidence interval, 1.2–6.2; P = 0.018). Despite medium-dose ICS, attenuated pore function predicted earlier exacerbations in incompletely controlled patients with moderate asthma (hazard ratio, 3.2; confidence interval, 1.1–9.3; P = 0.033). After establishing control with low-dose ICS in patients with mild asthma, those with attenuated pore function had more asthma symptoms, rescue albuterol use, and FEV1 reversal (P < 0.001, 0.03, and 0.03, respectively) during the ICS adjustment phase. Conclusions: P2X7 pore function protects against exacerbations of asthma and loss of control, independent of baseline severity and the maintenance therapy. PMID:23144325

7 CFR 652.7 - Quality assurance.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Quality assurance. 652.7 Section 652.7 Agriculture... assurance. (a) NRCS will review, in consultation with the Farm Service Agency, as appropriate, the quality... information obtained through its quality assurance process, documentation submitted by the technical service...

7 CFR 989.7 - Golden Seedless raisins.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Golden Seedless raisins. 989.7 Section 989.7... GROWN IN CALIFORNIA Order Regulating Handling Definitions § 989.7 Golden Seedless raisins. Golden Seedless raisins means raisins, the production of which includes soda dipping, sulfuring, and artificial...

7 CFR 932.7 - Variety group 2.

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2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Variety group 2. 932.7 Section 932.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 932.7 Variety group 2. Variety group 2 means the following varieties and...

7 CFR 982.7 - To handle.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false To handle. 982.7 Section 982.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... hazelnuts, inshell or shelled, into the channels of trade either within the area of production or from such...

The Drosophila Su(var)3-7 gene is required for oogenesis and female fertility, genetically interacts with piwi and aubergine, but impacts only weakly transposon silencing.

Science.gov (United States)

Basquin, Denis; Spierer, Anne; Begeot, Flora; Koryakov, Dmitry E; Todeschini, Anne-Laure; Ronsseray, Stéphane; Vieira, Cristina; Spierer, Pierre; Delattre, Marion

2014-01-01

Heterochromatin is made of repetitive sequences, mainly transposable elements (TEs), the regulation of which is critical for genome stability. We have analyzed the role of the heterochromatin-associated Su(var)3-7 protein in Drosophila ovaries. We present evidences that Su(var)3-7 is required for correct oogenesis and female fertility. It accumulates in heterochromatic domains of ovarian germline and somatic cells nuclei, where it co-localizes with HP1. Homozygous mutant females display ovaries with frequent degenerating egg-chambers. Absence of Su(var)3-7 in embryos leads to defects in meiosis and first mitotic divisions due to chromatin fragmentation or chromosome loss, showing that Su(var)3-7 is required for genome integrity. Females homozygous for Su(var)3-7 mutations strongly impair repression of P-transposable element induced gonadal dysgenesis but have minor effects on other TEs. Su(var)3-7 mutations reduce piRNA cluster transcription and slightly impact ovarian piRNA production. However, this modest piRNA reduction does not correlate with transposon de-silencing, suggesting that the moderate effect of Su(var)3-7 on some TE repression is not linked to piRNA production. Strikingly, Su(var)3-7 genetically interacts with the piwi and aubergine genes, key components of the piRNA pathway, by strongly impacting female fertility without impairing transposon silencing. These results lead us to propose that the interaction between Su(var)3-7 and piwi or aubergine controls important developmental processes independently of transposon silencing.

7 CFR 612.7 - Forecast user responsibility.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Forecast user responsibility. 612.7 Section 612.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE CONSERVATION OPERATIONS SNOW SURVEYS AND WATER SUPPLY FORECASTS § 612.7 Forecast user responsibility. The forecast use...

Cancer cell-associated cytoplasmic B7–H4 is induced by hypoxia through hypoxia-inducible factor-1α and promotes cancer cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Jeon, You-Kyoung [Department of Microbiology and Immunology, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Park, Sae-Gwang; Choi, Il-Whan [Department of Microbiology and Immunology, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Lee, Soo-Woong [Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Lee, Sang Min [Department of Internal Medicine, Division of Hematology/Oncology, Busan Paik Hospital, Inje University, Busan 614-735 (Korea, Republic of); Choi, Inhak, E-mail: miccih@inje.ac.kr [Department of Microbiology and Immunology, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, Busan 614-735 (Korea, Republic of)

2015-04-03

Aberrant B7–H4 expression in cancer tissues serves as a novel prognostic biomarker for poor survival in patients with cancer. However, the factor(s) that induce cancer cell-associated B7–H4 remain to be fully elucidated. We herein demonstrate that hypoxia upregulates B7–H4 transcription in primary CD138{sup +} multiple myeloma cells and cancer cell lines. In support of this finding, analysis of the Multiple Myeloma Genomics Portal (MMGP) data set revealed a positive correlation between the mRNA expression levels of B7–H4 and the endogenous hypoxia marker carbonic anhydrogenase 9. Hypoxia-induced B7–H4 expression was detected in the cytoplasm, but not in cancer cell membranes. Chromatin immunoprecipitation analysis demonstrated binding of hypoxia-inducible factor-1α (HIF-1α) to proximal hypoxia-response element (HRE) sites within the B7–H4 promoter. Knockdown of HIF-1α and pharmacological inhibition of HIF-1α diminished B7–H4 expression. Furthermore, knockdown of cytoplasmic B7–H4 in MCF-7 decreased the S-phase cell population under hypoxia. Finally, MMGP analysis revealed a positive correlation between the transcript levels of B7–H4 and proliferation-related genes including MKI67, CCNA1, and Myc in several patients with multiple myeloma. Our results provide insight into the mechanisms underlying B7–H4 upregulation and its role in cancer cell proliferation in a hypoxic tumor microenvironment. - Highlights: • Hypoxia upregulates B7–H4 transcription and protein expression. • Hypoxia-induced B7–H4 is detected in the cytoplasm, but not on membrane. • ChIP assay reveals a binding of HIF-1α to B7–H4 promoter at HRE site. • Knockdown and pharmacological inhibition of HIF-1α reduce B7–H4 expression. • B7–H4 knockdown decrease the number of cells in S-phase of cell cycle.

7 CFR 1714.7 - Interest rate cap.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Interest rate cap. 1714.7 Section 1714.7 Agriculture... PRE-LOAN POLICIES AND PROCEDURES FOR INSURED ELECTRIC LOANS General § 1714.7 Interest rate cap. Except... section, or both the rate disparity test for the interest rate cap and the consumer income test set forth...

The IgV domain of human B7-2 (CD86) is sufficient to co-stimulate T lymphocytes and induce cytokine secretion.

Science.gov (United States)

Rennert, P; Furlong, K; Jellis, C; Greenfield, E; Freeman, G J; Ueda, Y; Levine, B; June, C H; Gray, G S

1997-06-01

B7-1 (CD80) and B7-2 (CD86) are genetically and structurally related molecules expressed on antigen-presenting cells. Both bind CD28 to co-stimulate T lymphocytes, resulting in proliferation and cytokine production. The extracellular portions of B7-1 and B7-2 which bind to CD28 and CTLA-4 are related to Ig variable (V) and Ig constant (C) domain sequences. Recent reports have described splice variant forms of B7 proteins which occur in vivo and are of unknown function. Here we describe soluble recombinant forms of B7-1 and B7-2 containing either both of the Ig-like extracellular domains or the individual IgV or IgC domains coupled to an Ig Fc tail. Soluble B7-1 and B7-2 bind to CD28 and CTLA-4, and effectively co-stimulate T lymphocytes resulting in their proliferation and the secretion of cytokines. Furthermore, the IgV domain of B7-2 binds CD28 and CTLA-4, competes with B7-1 and B7-2 for binding to these receptors, and co-stimulates T lymphocytes. Cross-linked soluble B7-2v was the most potent co-stimulatory molecule tested and was active at a concentration approximately 100-fold lower than cross-linked soluble B7-1 or B7-2 proteins. When bound to tosyl-activated beads, B7-2v was capable of sustaining multiple rounds of T cell expansion. These data complement the description of naturally occurring variants to suggest that T cell co-stimulation in vivo may be regulated by soluble or truncated forms of B7 proteins.

Type 2 diabetes gene TCF7L2 polymorphism is not associated with fetal and postnatal growth in two birth cohort studies

Directory of Open Access Journals (Sweden)

Hofman Albert

2009-07-01

Full Text Available Abstract Background An inverse association between birth weight and the risk of developing type 2 diabetes (T2D in adulthood has been reported. This association may be explained by common genetic variants related to insulin secretion and resistance, since insulin is the most important growth factor in fetal life. The objective of this study was to examine whether T2D gene polymorphism TCF7L2 rs7903146 is associated with growth patterns from fetal life until infancy. Methods This study was performed in two independent birth cohort studies, one prospective population-based (Generation R, and one of subjects born small-for-gestational-age (SGA cohort. Fetal growth was assessed by ultrasounds in second and third trimesters of pregnancy in Generation R. Growth in infancy was assessed in both cohorts at birth and at 6, 12 and 24 months postnatally. TCF7L2 genotype was determined in 3,419 subjects in Generation R and in 566 subjects in the SGA cohort. Results Minor allele frequency did not differ significantly (p = 0.47 between Generation R (T-allele: 28.7% and the SGA cohort (T-allele: 29.8%. No differences at birth were found in gestational age or size (head circumference, length, weight between the genotypes in either cohort. TCF7L2 genotype was also not associated with any pre- or postnatal growth characteristic in either Generation R or the SGA cohort. Conclusion We found no evidence for an association between TCF7L2 genotype and fetal and early postnatal growth. Furthermore, this TCF7L2 polymorphism was not associated with an increased risk of SGA.

7 CFR 240.7 - Payments to States.

Science.gov (United States)

2010-01-01

... designated State Officials of a Payment Voucher on Letter of Credit (Treasury Form GFO 7578) in accordance... 7 Agriculture 4 2010-01-01 2010-01-01 false Payments to States. 240.7 Section 240.7 Agriculture... CHILD NUTRITION PROGRAMS CASH IN LIEU OF DONATED FOODS § 240.7 Payments to States. (a) Funds to be paid...

Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-κB regulation

Science.gov (United States)

Tokunaga, Fuminori; Nishimasu, Hiroshi; Ishitani, Ryuichiro; Goto, Eiji; Noguchi, Takuya; Mio, Kazuhiro; Kamei, Kiyoko; Ma, Averil; Iwai, Kazuhiro; Nureki, Osamu

2012-01-01

LUBAC (linear ubiquitin chain assembly complex) activates the canonical NF-κB pathway through linear polyubiquitination of NEMO (NF-κB essential modulator, also known as IKKγ) and RIP1. However, the regulatory mechanism of LUBAC-mediated NF-κB activation remains elusive. Here, we show that A20 suppresses LUBAC-mediated NF-κB activation by binding linear polyubiquitin via the C-terminal seventh zinc finger (ZF7), whereas CYLD suppresses it through deubiquitinase (DUB) activity. We determined the crystal structures of A20 ZF7 in complex with linear diubiquitin at 1.70–1.98 Å resolutions. The crystal structures revealed that A20 ZF7 simultaneously recognizes the Met1-linked proximal and distal ubiquitins, and that genetic mutations associated with B cell lymphomas map to the ubiquitin-binding sites. Our functional analysis indicated that the binding of A20 ZF7 to linear polyubiquitin contributes to the recruitment of A20 into a TNF receptor (TNFR) signalling complex containing LUBAC and IκB kinase (IKK), which results in NF-κB suppression. These findings provide new insight into the regulation of immune and inflammatory responses. PMID:23032187

Let-7b is involved in the inflammation and immune responses associated with Helicobacter pylori infection by targeting Toll-like receptor 4.

Directory of Open Access Journals (Sweden)

Gui-gen Teng

Full Text Available OBJECTIVES: Toll-like receptors (TLRs are important initiators in native immune responses to microbial infections. TLR4 is up-regulated in response to H.pylori infection in gastric epithelial cells. However, the regulatory mechanisms for the expression of TLR4 in H.pylori infection have not been clearly defined. The aims of this study are to present the evidence that microRNA let-7b directly regulates TLR4 expression in human gastric epithelial cells, and subsequently influences the activation of NF-κB and the expression of the downstream genes in H.pylori infection. METHODS: The expression of let-7b was determined in gastric mucosa specimens and in two gastric epithelial cell lines using quantitative RT-PCR. The expression of TLR4 was determined by immunohistochemistry staining and RT-PCR. The potential target of let-7b was identified by luciferase reporter assay and Western blot. Let-7b mimics and inhibitors were used to examine the effects of let-7b on NF-κB activity. The expression of the downstream genes of NF-κB was also determined in cells infected with H.pylori 26695. RESULTS: Let-7b was significantly decreased in gastric mucosa specimens and in gastric epithelial cell lines (AGS, GES-1 infected with H.pylori 26695 (cagA+. Let-7b was complementary to the 3'-UTR of TLR4 mRNA and regulated TLR4 expression via post-transcriptional suppression in gastric epithelium. Infection of H.pylori induced the expression of TLR4 and activated NF-κB in AGS and GES-1 cells. Overexpression of let-7b by mimics downregulated TLR4, and subsequently attenuated NF-κB, MyD88, NF-κB1/p50, RelA/p65. The expression of IL-8, COX-2 and CyclinD1 was inhibited in H.pylori infected cells with let-7b overexpression. Both TAK-242 (TLR4 inhibitor and SN50 (NF-κB inhibitor significantly inhibited the H.pylori induced downregulation of let-7b. CONCLUSIONS: Let-7b targets at TLR4 mRNA, and regulates the activation of NF-κB and the expression of the downstream genes

Dental caries is negatively correlated with body mass index among 7-9 years old children in Guangzhou, China.

Science.gov (United States)

Liang, Jing-Jing; Zhang, Zhe-Qing; Chen, Ya-Jun; Mai, Jin-Cheng; Ma, Jun; Yang, Wen-Han; Jing, Jin

2016-07-26

Evidence linking caries in primary dentition and children's anthropometric measures is contradictory. We aimed to evaluate the prevalence of primary dental caries and its relationship with body mass index (BMI) among 7-9 years old school children in urban Guangzhou, China. This cross-sectional study enrolled 32,461 pupils (14,778 girls and 17,683 boys) aged 7-9 years from 65 elementary schools in Guangzhou. Dental caries was detected according to criteria recommended by the World Health Organization (WHO). The total mean decayed, missing or filled teeth (dmft) of primary dentition were assessed. Weight and height were measured and BMI was calculated. Children were classified into underweight, normal weight, overweight and obesity groups by BMI based on Chinese criteria. Z-score of BMI-for-age (BAZ) was calculated by WHO standardized procedure. Multivariable odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using logistic regression. Restricted cubic spline regression was applied to evaluate the shape of the relationship between BAZ and primary dental caries. The prevalence of primary dental caries was 30.7 % in total sample. Regarding dmft values, the mean ± standard deviation (SD) in the combined sample were 1.03 ± 2.05 in boys and 0.93 ± 1.92 in girls. Both indices decreased by age. Compared with normal BMI group, children in overweight and obesity groups have 27 % (OR = 0.73, 95 % CI: 0.66-0.81, P caries after adjustment for age and gender, respectively. Although in general, increased BAZ was associated with decreased risk of dental caries, full-range BAZ was associated with dental caries in an A-shaped manner with a zenith at around -1.4. Higher BMI was associated with lower odds of caries; overweight and obese children were more likely to be primary dental caries free among 7-9 years in Guangzhou, China.

Java EE 7 handbook

CERN Document Server

Pilgrim, Peter A

2013-01-01

Java EE 7 Handbook is an example based tutorial with descriptions and explanations.""Java EE 7 Handbook"" is for the developer, designer, and architect aiming to get acquainted with the Java EE platform in its newest edition. This guide will enhance your knowledge about the Java EE 7 platform. Whether you are a long-term Java EE (J2EE) developer or an intermediate level engineer on the JVM with just Java SE behind you, this handbook is for you, the new contemporary Java EE 7 developer!

The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients

DEFF Research Database (Denmark)

Marcos, Séverine; Sarfati, Julie; Leroy, Chrystel

2014-01-01

CONTEXT: Mutations in CHD7, a gene previously implicated in CHARGE (coloboma, heart defect, choanal atresia, retardation of growth and/or development, genital hypoplasia, ear anomalies) syndrome, have been reported in patients presenting with Kallmann syndrome (KS) or congenital hypogonadotropic...... hypogonadism (CHH). Most mutations causing CHARGE syndrome result in premature stop codons and occur de novo, but the proportion of truncating vs nontruncating mutations in KS and CHH patients is still unknown. OBJECTIVE: The objective of the study was to determine the nature, prevalence, mode of transmission......, and clinical spectrum of CHD7 mutations in a large series of patients. DESIGN: We studied 209 KS and 94 CHH patients. These patients had not been diagnosed with CHARGE syndrome according to the current criteria. We searched for mutations in 16 KS and CHH genes including CHD7. RESULTS: We found presumably...

Application of FISH 7q in MDS patients without monosomy 7 or 7q deletion by conventional G-banding cytogenetics: does -7/7q- detection by FISH have prognostic value?

Science.gov (United States)

Ademà, Vera; Hernández, Jesús María; Abáigar, María; Lumbreras, Eva; Such, Esperanza; Calull, Anna; Dominguez, Esther; Arenillas, Leonor; Mallo, Mar; Cervera, José; Marugán, Isabel; Tormo, Mar; García, Francisca; González, Teresa; Luño, Elisa; Sanzo, Carmen; Martín, María Luisa; Fernández, Manuela; Costa, Dolors; Blázquez, Beatriz; Barreña, Beatriz; Marco, Fernando; Batlle, Ana; Buño, Ismael; Martínez-Laperche, Carolina; Noriega, Víctor; Collado, Rosa; Ivars, David; Carbonell, Félix; Vallcorba, Isabel; Melero, Josefa; Delgado, Elena; Vargas, María Teresa; Grau, Javier; Salido, Marta; Espinet, Blanca; Melero, Carme; Florensa, Lourdes; Pedro, Carmen; Solé, Francesc

2013-04-01

Chromosomal abnormalities are detected in 40-60% of patients with de novo myelodysplastic syndromes (MDS). This study used the FISH technique in 773 patients with de novo MDS without evidence of monosomy 7 (-7) or 7q deletion (7q-) by conventional G-banding cytogenetics (CC) to analyze their prognostic impact by FISH alone. FISH detected -7/7q- in 5.2% of patients. Presence of -7/7q- was associated with shorter overall survival than absence of such aberrations. Our results suggest that FISH 7q could be beneficial in patients with intermediate WHO morphologic risk stratification and no evidence of -7/7q- by CC. Copyright © 2012 Elsevier Ltd. All rights reserved.

Non-homologous end joining pathway is the major route of protection against 4β-hydroxywithanolide E-induced DNA damage in MCF-7 cells.

Science.gov (United States)

You, B-J; Wu, Y-C; Lee, C-L; Lee, H-Z

2014-03-01

4β-Hydroxywithanolide E is a bioactive withanolide extracted from Physalis peruviana. 4β-Hydroxywithanolide E caused reactive oxygen species production and cell apoptosis in human breast cancer MCF-7 cells. We further found that 4β-hydroxywithanolide E induced DNA damage and regulated the DNA damage signaling in MCF-7 cells. The DNA damage sensors and repair proteins act promptly to remove DNA lesions by 4β-hydroxywithanolide E. The ataxia-telangiectasia mutated protein (ATM)-dependent DNA damage signaling pathway is involved in 4β-hydroxywithanolide E-induced apoptosis of MCF-7 cells. Non-homologous end joining pathway, but not homologous recombination, is the major route of protection of MCF-7 cells against 4β-hydroxywithanolide E-induced DNA damage. 4β-Hydroxywithanolide E had no significant impact on the base excision repair pathway. In this study, we examined the 4β-hydroxywithanolide E-induced DNA damage as a research tool in project investigating the DNA repair signaling in breast cancer cells. We also suggest that 4β-hydroxywithanolide E assert its anti-tumor activity in carcinogenic progression and develop into a dietary chemopreventive agent. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association with the Plasma Membrane Is Sufficient for Potentiating Catalytic Activity of Regulators of G Protein Signaling (RGS) Proteins of the R7 Subfamily.

Science.gov (United States)

Muntean, Brian S; Martemyanov, Kirill A

2016-03-25

Regulators of G protein Signaling (RGS) promote deactivation of heterotrimeric G proteins thus controlling the magnitude and kinetics of responses mediated by G protein-coupled receptors (GPCR). In the nervous system, RGS7 and RGS9-2 play essential role in vision, reward processing, and movement control. Both RGS7 and RGS9-2 belong to the R7 subfamily of RGS proteins that form macromolecular complexes with R7-binding protein (R7BP). R7BP targets RGS proteins to the plasma membrane and augments their GTPase-accelerating protein (GAP) activity, ultimately accelerating deactivation of G protein signaling. However, it remains unclear if R7BP serves exclusively as a membrane anchoring subunit or further modulates RGS proteins to increase their GAP activity. To directly answer this question, we utilized a rapidly reversible chemically induced protein dimerization system that enabled us to control RGS localization independent from R7BP in living cells. To monitor kinetics of Gα deactivation, we coupled this strategy with measuring changes in the GAP activity by bioluminescence resonance energy transfer-based assay in a cellular system containing μ-opioid receptor. This approach was used to correlate changes in RGS localization and activity in the presence or absence of R7BP. Strikingly, we observed that RGS activity is augmented by membrane recruitment, in an orientation independent manner with no additional contributions provided by R7BP. These findings argue that the association of R7 RGS proteins with the membrane environment provides a major direct contribution to modulation of their GAP activity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

PENGGUNAAN MAKROZOOBENTOS SEBAGAI INDIKATOR STATUS PERAIRAN HULU SUNGAI CISADANE, BOGOR

Directory of Open Access Journals (Sweden)

Dyah Muji Rahayu

2015-04-01

Full Text Available Anthropogenic pollution (organic matter and Hg around Cisadane River upstream can affect the abundances of macrozoobenthos. The aim of this research was to identify the abundances of macrozoobenthos and feeding groups, and also to identify the status of waters based on macrozoobenthos community. The research was conducted on January to March in four locations in the upstream of Cisadane River, covering Cikuluwung (ST 1, Cisarua (ST 2, Curug Bitung (ST 3, and Lukut (ST 4. Samples were collected with kick net and Eckman Grab. The dominance macrozoobenthos are Bungona (171 ind/m2, Simulium (101 ind/m2, Cheumatopsyche (50 ind/m2, and Polypedilum (28 ind/m2. Based on feeding groups, the dominance are filtering collector and gatherer collector. Based on the Pollution Index and Heavy Metal Pollution Index (Hg on sediment, the upstream of Cisadane River is low polluted whereas EPT Index and Signal showed that upstream of Cisadane River is moderate polluted.

Mastering Windows 7 Deployment

CERN Document Server

Finn, Aidan; van Surksum, Kenneth

2011-01-01

Get professional-level instruction on Windows 7 deployment tools Enterprise-level operating system deployment is challenging and requires knowledge of specific tools. It is expected that Windows 7 will be extensively deployed in businesses worldwide. This comprehensive Sybex guide provides thorough coverage of the Microsoft deployment tools that were specifically created for Windows 7, preparing system administrators, MIS professionals, and corporate programmers to tackle the task effectively.Companies worldwide are expected to deploy Windows 7 as their enterprise operating system; system admi

Spinal cord pathology is ameliorated by P2X7 antagonism in a SOD1-mutant mouse model of amyotrophic lateral sclerosis

Directory of Open Access Journals (Sweden)

Savina Apolloni

2014-09-01

Full Text Available In recent years there has been an increasing awareness of the role of P2X7, a receptor for extracellular ATP, in modulating physiopathological mechanisms in the central nervous system. In particular, P2X7 has been shown to be implicated in neuropsychiatry, chronic pain, neurodegeneration and neuroinflammation. Remarkably, P2X7 has also been shown to be a ‘gene modifier’ in amyotrophic lateral sclerosis (ALS: the receptor is upregulated in spinal cord microglia in human and rat at advanced stages of the disease; in vitro, activation of P2X7 exacerbates pro-inflammatory responses in microglia that have an ALS phenotype, as well as toxicity towards neuronal cells. Despite this detrimental in vitro role of P2X7, in SOD1-G93A mice lacking P2X7, the clinical onset of ALS was significantly accelerated and disease progression worsened, thus indicating that the receptor might have some beneficial effects, at least at certain stages of disease. In order to clarify this dual action of P2X7 in ALS pathogenesis, in the present work we used the antagonist Brilliant Blue G (BBG, a blood-brain barrier permeable and safe drug that has already been proven to reduce neuroinflammation in traumatic brain injury, cerebral ischemia-reperfusion, neuropathic pain and experimental autoimmune encephalitis. We tested BBG in the SOD1-G93A ALS mouse model at asymptomatic, pre-symptomatic and late pre-symptomatic phases of disease. BBG at late pre-onset significantly enhanced motor neuron survival and reduced microgliosis in lumbar spinal cord, modulating inflammatory markers such as NF-κB, NADPH oxidase 2, interleukin-1β, interleukin-10 and brain-derived neurotrophic factor. This was accompanied by delayed onset and improved general conditions and motor performance, in both male and female mice, although survival appeared unaffected. Our results prove the twofold role of P2X7 in the course of ALS and establish that P2X7 modulation might represent a promising

45 CFR 7.7 - Notice to employee of determination.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Notice to employee of determination. 7.7 Section 7.7 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION EMPLOYEE INVENTIONS § 7.7 Notice to employee of determination. The employee-inventor shall be notified in writing of the...

Drycleaner Database - Region 7

Data.gov (United States)

U.S. Environmental Protection Agency — THIS DATA ASSET NO LONGER ACTIVE: This is metadata documentation for the Region 7 Drycleaner Database (R7DryClnDB) which tracks all Region7 drycleaners who notify...

Preparation and characterization of three 7Be targets for the measurement of the 7Be(n, p)7Li and 7Be(n, α)7Li reaction cross sections

Science.gov (United States)

Maugeri, E. A.; Heinitz, S.; Dressler, R.; Barbagallo, M.; Ulrich, J.; Schumann, D.; Colonna, N.; Köster, U.; Ayranov, M.; Vontobel, P.; Mastromarco, M.; Schell, J.; Correia, J. Martins; Stora, T.; n TOF Collaboration

2018-05-01

This manuscript describes the production of three targets obtained by implantation of different activities of 7Be into thin aluminium disks. Two of the produced targets were used to measure the 7Be(n, p)7Li cross section in the energy range of interest for the Big-Bang Nucleosynthesis. A third target was used to measure the cross sections of 7Be(n, p)7Li and 7Be(n, α)7Li nuclear reactions with cold and thermal neutrons, respectively. This paper describes also the characterization of the first two targets, performed after the neutron irradiation, in terms of implanted 7Be activities and spatial distributions.

IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

Directory of Open Access Journals (Sweden)

Tae Sik Goh

2017-01-01

Full Text Available IL-7 signaling via IL-7Rα and common γ-chain (γc is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα.

IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

Science.gov (United States)

Goh, Tae Sik; Jo, Yuna; Lee, Byunghyuk; Kim, Geona; Hwang, Hyunju; Ko, Eunhee; Kang, Seung Wan; Oh, Sae-Ock; Baek, Sun-Yong; Yoon, Sik; Lee, Jung Sub

2017-01-01

IL-7 signaling via IL-7Rα and common γ-chain (γc) is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα. PMID:28127156

Measurement of $^{7}$Be(n,$\\alpha$)$^{4}$He and $^{7}$Be(n,p)$^{7}$Li cross-sections for the Cosmological Lithium Problem

CERN Multimedia

We propose to measure in the second experimental area of n TOF the $^{7}$Be(n,$\\alpha$)$^{4}$He and $^{7}$Be(n,p)$^{7}$Li reaction in a wide energy range. Both reactions are of interest for the long- standing "Cosmological $^{7}$Li problem" in Big Bang Nucleosynthesis (BBN). The very high specific activity of $^{7}$Be, and the low cross section of the (n,$\\alpha$) reaction make this measurement extremely dicult. As afirst step, we request some beam time for detector tests at EAR2. For the $^{7}$Be(n,p) reaction, previously measured up to 13 keV, the diculty is mostly associated withthe availability of a high-purity $^{7}$Be sample. To this purpose we ask for three shifts of offline ISOLDE mass separation for the preparation of the sample to be used at n TOF. To this end, a prior endorsement by INTC of the scientific validity and feasibility of the proposed measurement is requested, to start activity on the sample production. The present proposal is part of a wider collaborative effort aimed at measuring neutr...

7 CFR 945.7 - Certified seed potatoes.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Certified seed potatoes. 945.7 Section 945.7... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN CERTAIN... Certified seed potatoes. Certified seed potatoes means and includes all potatoes officially certified and...

Inhibition of the Ras-ERK pathway in mitotic COS7 cells is due to the inability of EGFR/Raf to transduce EGF signaling to downstream proteins.

Science.gov (United States)

Shi, Huaiping; Zhang, Tianying; Yi, Yongqing; Ma, Yue

2016-06-01

Although previous studies have shown that Ras-ERK signaling in mitosis is closed due to the inhibition of signal transduction, the events involved in the molecular mechanisms are still unclear. In the present study, we investigated the Ras-ERK signaling pathway in mitotic COS7 cells. The results demonstrated that treatment with epidermal growth factor (EGF) failed to increase the endocytosis of EGF-EGFR (EGF receptor) complexes in mitotic COS7 cells, although a large amount of endosomes were found in asynchronous COS7 cells. Clathrin expression levels in mitotic COS7 cells were inhibited whereas caveolin expression levels in mitotic COS7 cells were almost unaffected. Y1068 and Y1086 residues of EGFR in the mitotic COS7 cells were activated. However, Grb2 and Shc in the mitotic COS7 cells did not bind to activated EGFR. Ras activity was inhibited in the mitotic COS7 cells whereas its downstream protein, Raf, was obviously phosphorylated by EGF in mitosis. Treatment with phorbol 12-myristate 13-acetate (PMA) also increased the phosphorylation levels of Raf in the mitotic COS7 cells. Nevertheless, Raf phosphorylation in mitosis was significantly inhibited by AG1478. Lastly, activation of EGF-mediated MEK and ERK in the mitotic COS7 cells was obviously inhibited. In summary, our results suggest that the Ras-ERK pathway is inhibited in mitotic COS7 cells which may be the dual result of the difficulty in the transduction of EGF signaling by EGFR or Raf to downstream proteins.

7 CFR 1900.7 - Effect on other regulations.

Science.gov (United States)

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Effect on other regulations. 1900.7 Section 1900.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... REGULATIONS GENERAL Delegations of Authority § 1900.7 Effect on other regulations. This subpart does not...

Adenovirus 4/7 Vaccine's Effect on Disease Rates Is Associated With Disappearance of Adenovirus on Building Surfaces at a Military Recruit Base.

Science.gov (United States)

Broderick, Michael; Myers, Christopher; Balansay, Melinda; Vo, Scott; Osuna, Angel; Russell, Kevin

2017-11-01

Febrile respiratory illness resulting from adenovirus types 4 and 7 (Ad4/7) was endemic at military training camps, but controlled by an Ad4/7 vaccine from the 1970s to 1999, the year it was discontinued. Thereafter, rates returned to prevaccine levels. Rates dropped after reintroduction of an Ad4/7 vaccine in 2011. Surfaces of the barracks and medical clinic of a training camp were swabbed in 3 studies in 2004 and 1 study in 2007, and tested with culture and polymerase chain reaction (PCR). Similar swabbing was done in 2013 and 2015 and tested with PCR. In the studies before 2011 (prevaccine), 12% of samples were Ad4/7 positive by culture and 27% positive by PCR. In the 2 studies after 2011 (postvaccine), no samples were Ad4/7 positive. The Ad 4/7 vaccine has resulted in the near elimination of Ad4/7-related disease and the disappearance of Ad4/7 from surfaces in a military basic training camp. Renewed transmission of Ad4/7 in this setting would likely require new importation from military recruits and an immunologically naive cohort, which the current vaccination program prevents. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

The Drosophila Su(var)3–7 Gene Is Required for Oogenesis and Female Fertility, Genetically Interacts with piwi and aubergine, but Impacts Only Weakly Transposon Silencing

Science.gov (United States)

Begeot, Flora; Koryakov, Dmitry E.; Todeschini, Anne-Laure; Ronsseray, Stéphane; Vieira, Cristina; Spierer, Pierre; Delattre, Marion

2014-01-01

Heterochromatin is made of repetitive sequences, mainly transposable elements (TEs), the regulation of which is critical for genome stability. We have analyzed the role of the heterochromatin-associated Su(var)3–7 protein in Drosophila ovaries. We present evidences that Su(var)3–7 is required for correct oogenesis and female fertility. It accumulates in heterochromatic domains of ovarian germline and somatic cells nuclei, where it co-localizes with HP1. Homozygous mutant females display ovaries with frequent degenerating egg-chambers. Absence of Su(var)3–7 in embryos leads to defects in meiosis and first mitotic divisions due to chromatin fragmentation or chromosome loss, showing that Su(var)3–7 is required for genome integrity. Females homozygous for Su(var)3–7 mutations strongly impair repression of P-transposable element induced gonadal dysgenesis but have minor effects on other TEs. Su(var)3–7 mutations reduce piRNA cluster transcription and slightly impact ovarian piRNA production. However, this modest piRNA reduction does not correlate with transposon de-silencing, suggesting that the moderate effect of Su(var)3–7 on some TE repression is not linked to piRNA production. Strikingly, Su(var)3–7 genetically interacts with the piwi and aubergine genes, key components of the piRNA pathway, by strongly impacting female fertility without impairing transposon silencing. These results lead us to propose that the interaction between Su(var)3–7 and piwi or aubergine controls important developmental processes independently of transposon silencing. PMID:24820312

7 CFR 340.7 - Marking and identity.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Marking and identity. 340.7 Section 340.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE... identity. (a) Any regulated article to be imported other than by mail, shall, at the time of importation...

7 CFR 1499.7 - Transportation of goods.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Transportation of goods. 1499.7 Section 1499.7... Transportation of goods. (a) Shipments of donated commodities are subject to the requirements of 46 U.S.C. 55305 and 55314, regarding carriage on U.S.-flag vessels. (b) Transportation of donated commodities and...

7 CFR 1599.7 - Transportation of goods.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Transportation of goods. 1599.7 Section 1599.7... Transportation of goods. (a) Shipments of donated commodities are subject to the requirements of 46 U.S.C. 55305 and 55314, regarding carriage on U.S.-flag vessels. (b) Transportation of donated commodities and...

Vacquinol-1 inducible cell death in glioblastoma multiforme is counter regulated by TRPM7 activity induced by exogenous ATP.

Science.gov (United States)

Sander, Philip; Mostafa, Haouraa; Soboh, Ayman; Schneider, Julian M; Pala, Andrej; Baron, Ann-Kathrin; Moepps, Barbara; Wirtz, C Rainer; Georgieff, Michael; Schneider, Marion

2017-05-23

Glioblastomas (GBM) are the most malignant brain tumors in humans and have a very poor prognosis. New therapeutic options are urgently needed. A novel drug, Vacquinol-1 (Vac), a quinolone derivative, displays promising properties by inducing rapid cell death in GBM but not in non-transformed tissues. Features of this type of cell death are compatible with a process termed methuosis. Here we tested Vac on a highly malignant glioma cell line observed by long-term video microscopy. Human dental-pulp stem cells (DPSCs) served as controls. A major finding was that an exogenous ATP concentration of as little as 1 μM counter regulated the Vac-induced cell death. Studies using carvacrol, an inhibitor of transient receptor potential cation channel, subfamily M, member 7 (TRPM7), demonstrated that the ATP-inducible inhibitory effect is likely to be via TRPM7. Exogenous ATP is of relevance in GBM with large necrotic areas. Our results support the use of GBM cultures with different grades of malignancy to address their sensitivity to methuosis. The video-microscopy approach presented here allows decoding of signaling pathways as well as mechanisms of chemotherapeutic resistance by long-term observation. Before implementing Vac as a novel therapeutic drug in GBM, cells from each individual patient need to be assessed for their ATP sensitivity. In summary, the current investigation supports the concept of methuosis, described as non-apoptotic cell death and a promising approach for GBM treatment. Tissue-resident ATP/necrosis may interfere with this cell-death pathway but can be overcome by a natural compound, carvacrol that even penetrates the blood-brain barrier.

Variation in density of cattle-visiting muscid flies between Danish inland pastures

DEFF Research Database (Denmark)

Jensen, Karl-Martin Vagn; Jespersen, Jørgen B.; Nielsen, B. Overgaard

1993-01-01

recorded, whilst the relative abundance and density of the species and the total fly-load varied considerably between pastures. In most cases the mean loads of Haematobia irritans (L.) and Hydrotaea irritans (Fall.) on heifers varied significantly in relation to site topography and shelter. These crude......The density of cattle-visiting flies (Muscidae) and the load of black-flies (Simulium spp.) were estimated in twelve and eighteen inland pastures in Denmark in 1984 and 1985 respectively. No differences in the geographical distribution pattern of the predominant cattle-visiting Muscidae were...... site variables explained 65-98% of the variation in densities of horn flies and sheep head flies observed between pastures. Highest densities of Hydrotaea irritans were primarily associated with permanent, low-lying, fairly sheltered grassland sites, whereas the density was low in temporary, dry, wind...

The importance of the tensor interaction in the (7Li, 7Be) reaction

International Nuclear Information System (INIS)

Dodd, A.C.; Clarke, N.M.; Coopersmith, J.; Griffiths, R.J.; Pearce, K.I.; Stanley, B.; Cook, J.

1985-01-01

Data for the 28 Si( 7 Li, 7 Be) 28 Al reaction at 72 MeV and for the 26 Mg( 7 Li, 7 Be) 26 Na reaction at 88 MeV are presented together with one-step DWBA calculations using microscopic form factors. The tensor interaction is shown to be important to explain the structureless nature of the angular distributions. (author)

Mol 7C/6

International Nuclear Information System (INIS)

Aberle, J.; Schleisiek, K.; Schmuck, I.; Schmidt, L.; Romer, O.; Weih, G.

1995-01-01

The Mol 7C/6 coolant blockage experiment in the Belgian BR2 reactor yielded results different from Mol 7C experiments with low burnup pins: At 10% burnup local failure is not self-limiting, but requires active systems for detection and scram. The Mol 7C series was finished in 1991. In each of the test bundles Mol 7C/4, /5 and /6, 30 Mk I pins pre-irradiated in KNK II were used. The central blockage consisted of enriched UO 2 covering 30 percent of the bundle cross-section, with a height of 40 mm. The most important system for timely detection of coolant blockages of the type studied in Mol 7C/6 is based on DND. (orig.)

Multivariate time series analysis of SafetyNet data. SafetyNet, Building the European Road Safety Observatory, Workpackage 7, Deliverable 7.7.

NARCIS (Netherlands)

Commandeur, J.J.F. Bijleveld, F.D. & Bergel, R.

2009-01-01

This deliverable provides an application of theories and methods documented in Deliverables 7.4 and 7.5 of work package 7 of the SafetyNet project. In this deliverable, use of select analysis techniques is demonstrated through real world road safety analysis problems, using aggregate data which may

Circulating let-7g is down-regulated in Bernese Mountain dogs with disseminated histiocytic sarcoma and carcinomas

DEFF Research Database (Denmark)

Børresen, B; Nielsen, L N; Jessen, L R

2017-01-01

Cancer is a prevalent cause of mortality in Bernese mountain dogs (BMDs). Circulating microRNAs (miRNAs) are found in blood and have been identified as promising biomarkers in various neoplastic diseases in humans. In the current study, the expression profile of different types of mi...... dogs. Twenty-four different miRNAs were profiled from RNA isolated from whole blood preserved in PAXgene(®) tubes using quantitative real-time PCR (qPCR). The miRNA let-7g was significantly down-regulated in dogs with cancer (P = 0.002) and dogs with DHS (P = 0.011) compared with healthy controls...

Variation in WNT7A is unlikely to be a cause of familial Congenital Talipes Equinovarus

NARCIS (Netherlands)

Liu, Guoqing; Inglis, Julie; Cardy, Amanda; Shaw, Duncan; Sahota, Sukhy; Hennekam, Raoul; Sharp, Linda; Miedzybrodzka, Zosia

2008-01-01

Background: Genetic factors make an important contribution to the aetiology of congenital talipes equinovarus ( CTEV), the most common developmental disorder of the lower limb. WNT7A was suggested as a candidate gene for CTEV on the basis of a genome-wide scan for linkage in a large multi-case

The ADH7 Promoter of Saccharomyces cerevisiae is Vanillin-Inducible and Enables mRNA Translation Under Severe Vanillin Stress

OpenAIRE

Nguyen, Trinh T. M.; Iwaki, Aya; Izawa, Shingo

2015-01-01

Vanillin is one of the major phenolic aldehyde compounds derived from lignocellulosic biomass and acts as a potent fermentation inhibitor to repress the growth and fermentative ability of yeast. Vanillin can be reduced to its less toxic form, vanillyl alcohol, by the yeast NADPH-dependent medium chain alcohol dehydrogenases, Adh6 and Adh7. However, there is little information available regarding the regulation of their gene expression upon severe vanillin stress, which has been shown to repre...

Myxoma virus M-T7, a secreted homolog of the interferon-gamma receptor, is a critical virulence factor for the development of myxomatosis in European rabbits.

Science.gov (United States)

Mossman, K; Nation, P; Macen, J; Garbutt, M; Lucas, A; McFadden, G

1996-01-01

Myxoma virus is a leporipoxvirus of New World rabbits (Sylvilagus sp.) that induces a rapidly lethal infection known as myxomatosis in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, myxoma virus encodes a plethora of proteins to circumvent or inhibit a variety of host antiviral immune mechanisms. M-T7, the most abundantly secreted protein of myxoma virus-infected cells, was originally identified as an interferon-gamma receptor homolog (Upton, Mossman, and McFadden, Science 258, 1369-1372, 1992). Here, we demonstrate that M-T7 is dispensable for virus replication in cultured cells but is a critical virulence factor for virus pathogenesis in European rabbits. Disruption of both copies of the M-T7 gene in myxoma virus was achieved by the deletion of 372 bp of M-T7 coding sequences, replacement with a selectable marker, p7.5Ecogpt, and selection of a recombinant virus (vMyxlac-T7gpt) resistant to mycophenolic acid. vMyxlac-T7gpt expressed no detectable M-T7 protein and infected cells supernatants were devoid of any detectable interferon-gamma binding activities. Immunohistochemical staining with anti-beta-galactosidase and anti-CD43 antibodies demonstrated that in vMyxlac-T7gpt-infected rabbits the loss of M-T7 not only caused a dramatic reduction in disease symptoms and viral dissemination to secondary sites, but also dramatically influenced host leukocyte behavior. Notably, primary lesions in wild-type virus infections were generally underlayed by large masses of inflammatory cells that did not effectively migrate into the dermal sites of viral replication, whereas in vMyxlac-T7gpt infections this apparent block to leukocyte influx was relieved. A second major phenotypic distinction noted for the M-T7 knockout virus was the extensive activation of lymphocytes in secondary immune organs, particularly the spleen and lymph nodes, by Day 4 of the infection. This is in stark contrast to infection by wild-type myxoma virus, which results in relatively

Overexpression of nuclear AR-V7 protein in primary prostate cancer is an independent negative prognostic marker in men with high-risk disease receiving adjuvant therapy.

Science.gov (United States)

Chen, Xin; Bernemann, Christof; Tolkach, Yuri; Heller, Martina; Nientiedt, Cathleen; Falkenstein, Michael; Herpel, Esther; Jenzer, Maximilian; Grüllich, Carsten; Jäger, Dirk; Sültmann, Holger; Duensing, Anette; Perner, Sven; Cronauer, Marcus V; Stephan, Carsten; Debus, Jürgen; Schrader, Andres Jan; Kristiansen, Glen; Hohenfellner, Markus; Duensing, Stefan

2018-04-01

Overexpression of the androgen receptor (AR) splice variant 7 (AR-V7) has recently been reported to be associated with resistance to antihormonal therapy. Herein, we address the question whether tumor cells with AR-V7 expression can be detected at the time of radical prostatectomy, that is, before long-term hormonal manipulation and castration resistance, and what the potential prognostic impact on the biochemical recurrence (BCR)-free survival may be. An anti-AR-V7 antibody was first validated in a training set of prostate cancer specimens by a comparison of AR-V7 protein to AR-V7 mRNA expression. We then analyzed nuclear AR-V7 protein expression in the primary tumors and lymph node metastases from 163 predominantly high-risk patients (cohort I) as well as the primary tumors from patients of a second, consecutive patient cohort (n = 238, cohort II) not selected for any clinicopathological features. Staining results were correlated to patient characteristics and BCR-free patient survival. High nuclear AR-V7 protein expression was detected in approximately 30%-40% of patients in cohort I and II at the time of radical prostatectomy. High baseline expression of nuclear AR-V7 protein was associated with an unfavorable BCR-free survival in the high-risk patient cohort I but not in the unselected consecutive cohort II. Remarkably, AR-V7 was an independent negative prognostic factor in high-risk prostate cancer patients of cohort I who were selected to receive adjuvant treatment. Prostate cancer cells with high nuclear AR-V7 protein expression can be detected in a substantial proportion of tumors at the time of radical prostatectomy. The presence of AR-V7-positive tumor cells is associated with an unfavorable prognosis for BCR-free survival in a high-risk patient cohort including a subgroup of patients selected to receive adjuvant therapy, in which AR-V7 was an independent negative prognosticator. Overexpression of nuclear AR-V7 protein hence identifies a subset of tumors

A novel mutation in the MYO7A gene is associated with Usher syndrome type 1 in a Chinese family.

Science.gov (United States)

He, Xiaoguang; Peng, Qi; Li, Siping; Zhu, Pengyuan; Wu, Chunqiu; Rao, Chunbao; Lin, Jingqi; Lu, Xiaomei

2017-08-01

We aimed to investigate the genetic causes of hearing loss in a Chinese proband with autosomal recessive congenital deafness. The targeted capture of 159 known deafness genes and next-generation sequencing were performed to study the genetic causes of hearing loss in the Chinese family. Sanger sequencing was employed to verify the variant mutations in members of this family. The proband harbored two mutations in the MYO7A gene in the form of compound heterozygosity. She was found to be heterozygous for a novel insertion mutation c.3847_3848 ins TCTG (p.N1285LfsX24) in exon 30 and for the known mutation c.2239_2240delAG (p.R747S fsX16)in exon 19. The novel mutation was absent in the 1000 Genomes Project. These variants were carried in the heterozygous state by the parents and were therefore co-segregated with the genetic disease. Clinical re-assessment, including detailed audiologic and ocular examinations, revealed congenital deafness and retinitis pigmentosa in the proband. Collectively, the combination of audiometric, ophthalmologic and genetic examinations successfully confirmed the phenotype of Usher syndrome type 1 (USH1). This study demonstrates that the novel mutation c.3847_3848insTCTG (p. N1285LfsX24) in compound heterozygosity with c.2239_2240delAG in the MYO7A gene is the main cause of USH1 in the proband. Our study expands the mutational spectrum of MYO7A and provides a foundation for further investigations elucidating the MYO7A-related mechanisms of USH1. Copyright © 2017 Elsevier B.V. All rights reserved.

Straightforward synthesis of 2,2,4,4,5,7,7-d{sub 7}-cholestane: a new deuterated standard in petroleum analysis

Energy Technology Data Exchange (ETDEWEB)

Miranda, Maicon Guerra de; Albert, Andre Luis Mazzei; Cardoso, Jari Nobrega; Lopes, Rosangela Sabbatini Capella; Lopes, Claudio Cerqueira, E-mail: maicon_iq@yahoo.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Quimica

2013-10-01

A short and efficient synthesis of heptadeuterated 2,2,4,4,5,7,7-d7-cholestane (1) from cholesterol (3) is described. The deuterated material will be useful for the analysis of different sources of petroleum in analytical geochemistry laboratories as internal standard for quantification of steranes via gas chromatography-mass spectrometry (GC-MS). (author)

A Quantitative Trait Locus (LSq-1) on Mouse Chromosome 7 Is Linked to the Absence of Tissue Loss After Surgical Hindlimb Ischemia

Science.gov (United States)

Dokun, Ayotunde O.; Keum, Sehoon; Hazarika, Surovi; Li, Yongjun; Lamonte, Gregory M.; Wheeler, Ferrin; Marchuk, Douglas A.; Annex, Brian H.

2010-01-01

Background Peripheral arterial disease (PAD) caused by occlusive atherosclerosis of the lower extremity has 2 major clinical manifestations. Critical limb ischemia is characterized by rest pain and/or tissue loss and has a ≥40% risk of death and major amputation. Intermittent claudication causes pain on walking, has no tissue loss, and has amputation plus mortality rates of 2% to 4% per year. Progression from claudication to limb ischemia is infrequent. Risk factors in most PAD patients overlap. Thus, we hypothesized that genetic variations may be linked to presence or absence of tissue loss in PAD. Methods and Results Hindlimb ischemia (murine model of PAD) was induced in C57BL/6, BALB/c, C57BL/6×BALB/c (F1), F1×BALB/c (N2), A/J, and C57BL/6J-Chr7A/J/NaJ chromosome substitution strains. Mice were monitored for perfusion recovery and tissue necrosis. Genome-wide scanning with polymorphic markers across the 19 murine autosomes was performed on the N2 mice. Greater tissue loss and poorer perfusion recovery occurred in BALB/c than in the C57BL/6 strain. Analysis of 105 N2 progeny identified a single quantitative trait locus on chromosome 7 that exhibited significant linkage to both tissue necrosis and extent of perfusion recovery. Using the appropriate chromosome substitution strain, we demonstrate that C57BL/6-derived chromosome 7 is required for tissue preservation. Conclusions We have identified a quantitative trait locus on murine chromosome 7 (LSq-1) that is associated with the absence of tissue loss in a preclinical model of PAD and may be useful in identifying gene(s) that influence PAD in humans. PMID:18285563

7 CFR 1773.7 - Audit standards.

Science.gov (United States)

2010-01-01

... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Audit Requirements § 1773.7 Audit standards. (a) The audit must be performed in accordance with GAGAS and this part. The audit must be performed in accordance with GAGAS in effect at the audit date unless the borrower is directed otherwise, in writing, by RUS...

Intracellular calcium is a target of modulation of apoptosis in MCF-7 cells in the presence of IgA adsorbed to polyethylene glycol

Science.gov (United States)

Honorio-França, Adenilda Cristina; Nunes, Gabriel Triches; Fagundes, Danny Laura Gomes; de Marchi, Patrícia Gelli Feres; Fernandes, Rubian Trindade da Silva; França, Juliana Luzia; França-Botelho, Aline do Carmo; Moraes, Lucélia Campelo Albuquerque; Varotti, Fernando de Pilla; França, Eduardo Luzía

2016-01-01

Purpose Clinical and epidemiological studies have indicated that breastfeeding has a protective effect on breast cancer risk. Protein-based drugs, including antibodies, are being developed to attain better forms of cancer therapy. Secretory IgA (SIgA) is the antibody class in human breast milk, and its activity can be linked to the protective effect of breastfeeding. The aim of this study was to investigate the effect of polyethylene glycol (PEG) microspheres with adsorbed SIgA on MCF-7 human breast cancer cells. Methods The PEG microspheres were characterized by flow cytometry and fluorescence microscopy. The MCF-7 cells were obtained from American Type Culture Collection. MCF-7 cells were pre-incubated for 24 hours with or without SIgA (100 ng/mL), PEG microspheres or SIgA adsorbed in PEG microspheres (100 ng/mL). Viability, intracellular calcium release, and apoptosis in MCF-7 cells were determined by flow cytometry. Results Fluorescence microscopy and flow cytometry analyses revealed that SIgA was able to adsorb to the PEG microspheres. The MCF-7 cells that were incubated with PEG microspheres with adsorbed SIgA showed decreased viability. MCF-7 cells that were incubated with SIgA or PEG microspheres with adsorbed SIgA had increased intracellular Ca2+ levels. In the presence of SIgA, an increase in the percentage of apoptotic cells was observed. The highest apoptosis index was observed when the cells were treated with PEG microspheres with adsorbed SIgA. Conclusion These data suggest that colostral SIgA adsorbed to PEG microspheres has antitumor effects on human MCF-7 breast cancer cells and that the presence of large amounts of this protein in secreted breast milk may provide protection against breast tumors in women who breastfed. PMID:26893571

11 CFR 7.7 - Prohibited conduct-General.

Science.gov (United States)

2010-01-01

... Government efficiency or economy; (d) Losing independence or impartiality; (e) Making a Government decision... Employees or Commissioners § 7.7 Prohibited conduct—General. A Commissioner or employee shall avoid any...

Handbook of Accelerator Physics and Engineering (sections 2.7.1 - 2.7.5 and 7.6.2)

Energy Technology Data Exchange (ETDEWEB)

Roser, T.

1999-04-19

The sections written by this author are: 2.7.1- Thomas - BMT equation; 2.2.2- Spinor Algebra; 2.7.3- Spin Rotators and Siberian Snakes; 2.7.4- Ring with Spin Rotator and Siberian Snakes; 2.7.5- Depolarizing Resonances and Spin Flippers; & 7.6.2- Proton Beam Polarimeters

7 CFR 1124.7 - Pool plant.

Science.gov (United States)

2010-01-01

... agreement for other than Class I use) into ultra-pasteurized or aseptically-processed fluid milk products...) located within one or more States that require handlers to pay minimum prices for raw milk provided that... prices for raw milk. Subject to the following exclusions: (i) The plant is described in § 1124.7(a) or (b...

7 CFR 319.75-7 - Costs and charges.

Science.gov (United States)

2010-01-01

..., and shall be performed under the supervision of an inspector. Plant Protection and Quarantine will not... 7 Agriculture 5 2010-01-01 2010-01-01 false Costs and charges. 319.75-7 Section 319.75-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION...

7 CFR 7.10 - Conduct of county convention.

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2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Conduct of county convention. 7.10 Section 7.10 Agriculture Office of the Secretary of Agriculture SELECTION AND FUNCTIONS OF AGRICULTURAL STABILIZATION AND... other purpose. (e) The county committee shall give advance public notice of the county convention which...

7 CFR 7.6 - Determination of elective areas.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Determination of elective areas. 7.6 Section 7.6 Agriculture Office of the Secretary of Agriculture SELECTION AND FUNCTIONS OF AGRICULTURAL STABILIZATION AND... county committee shall give public notice of the community boundaries in advance of the election. ...

RELAP-7 Closure Correlations

Energy Technology Data Exchange (ETDEWEB)

Zou, Ling [Idaho National Lab. (INL), Idaho Falls, ID (United States); Berry, R. A. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Martineau, R. C. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Andrs, D. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Zhang, H. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hansel, J. E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Sharpe, J. P. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Johns, Russell C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-04-01

The RELAP-7 code is the next generation nuclear reactor system safety analysis code being developed at the Idaho National Laboratory (INL). The code is based on the INL’s modern scientific software development framework, MOOSE (Multi-Physics Object Oriented Simulation Environment). The overall design goal of RELAP-7 is to take advantage of the previous thirty years of advancements in computer architecture, software design, numerical integration methods, and physical models. The end result will be a reactor systems analysis capability that retains and improves upon RELAP5’s and TRACE’s capabilities and extends their analysis capabilities for all reactor system simulation scenarios. The RELAP-7 code utilizes the well-posed 7-equation two-phase flow model for compressible two-phase flow. Closure models used in the TRACE code has been reviewed and selected to reflect the progress made during the past decades and provide a basis for the colure correlations implemented in the RELAP-7 code. This document provides a summary on the closure correlations that are currently implemented in the RELAP-7 code. The closure correlations include sub-grid models that describe interactions between the fluids and the flow channel, and interactions between the two phases.

7 CFR 760.7 - Other requirements for affected farmers.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Other requirements for affected farmers. 760.7 Section... Payments to Dairy Farmers for Milk § 760.7 Other requirements for affected farmers. An indemnity payment for milk may be made under this subpart to an affected farmer only under the following conditions: (a...

7 CFR 772.7 - Leasing minor program loan security.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Leasing minor program loan security. 772.7 Section 772..., DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS SERVICING MINOR PROGRAM LOANS § 772.7 Leasing minor program loan security. (a) Eligibility. The Agency may consent to the borrower leasing all or a portion of security...

Ab-initio study of pure sup 7 sup 7 Se and sup 1 sup 2 sup 5 Te systems and of the sup 7 sup 7 Se nuclear quadrupole interaction in tellurium

CERN Document Server

Oh, Y K; Cho, H S

1999-01-01

Using the Hartree-Fock cluster procedure, we have studied the electric-field gradient tensors at the nuclear sites of sup 7 sup 7 Se and sup 1 sup 2 sup 5 Te in pure sup 1 sup 2 sup 5 Te systems and in tellurium crystalline system's with a sup 7 sup 7 Se impurity. From the results for the pure systems, sup 7 sup 7 Se in selenium and sup 1 sup 2 sup 5 Te in tellurium, using the observed quadrupole moments: Q( sup 7 sup 7 Se) 0.75 +- 0.07 barns and Q( sup 1 sup 2 sup 5 Te) = 0.35 +- 0.04 barns. Comparison is made with earlier values obtained by different methods. Using our calculated values of Q and the results of a study of the field-gradient tensors for sup 7 sup 7 Se in tellurium, the theoretical values of the quadrupole coupling constants are found to agree, within about 7 percent, with experiment. The calculated asymmetry parameters are also found to be in reasonable agreement with the experiment values, although the agreement not as close as in the case of the quadrupole -coupling constants. Directions fo...

Search for a resonant enhancement of the 7Be + d reaction and primordial 7Li abundances

International Nuclear Information System (INIS)

O'Malley, Patrick; Adekola, A.S.; Cizewski, J.A.; Howard, M.E.; Strauss, S.; Bardayan, Daniel W.; Chae, Kyung Yuk; Nesaraja, Caroline D.; Pain, Steven D.; Smith, Michael Scott; Ahn, S.H.; Jones, K.L.; Pittman, S.T.; Schmitt, Kyle; Graves, S.; Kozub, R.L.; Shriner, J.F. Jr.; Wheeler, J.L.; Linhardt, Laura; Matos, M.; Moazen, B.M.; Peters, W.A.; Spassova, I.

2011-01-01

Big Bang nucleosynthesis calculations, constrained by the Wilkinson Microwave Anisotropy Probe results, produce 7 Li abundances almost a factor of four larger than those extrapolated from observations. Since primordial 7 Li is believed to be mostly produced by the beta decay of 7 Be, one proposed solution to this discrepancy is a resonant enhancement of the 7 Be(d,p)2α reaction rate through the 5/2 + 16.7-MeV state in 9 B. The 2 H( 7 Be,d) 7 Be reaction was used to search for such a resonance; none was observed. An upper limit on the width of the proposed resonance was deduced.

7 CFR 319.55-7 - Importations by mail.

Science.gov (United States)