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  • 1
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    Using Bio-Chemistry Genetics Markers to Distinguish Barbus in Khozestan (2018)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    Details
    Publication Date: 2021-05-19
    Description: 0Genetic polymorphism by means of biochemical genetic markers using polyacrylamide gel electrophoresis system in four barbus fish species has been investigated. Species scientific name were Barbus sharpeyi ; Gunther, 1847 , Barbus grypus ; Heckel, 1843, Barbus xanthopterus ; Heckel, 1843 and Barbus esocinus ; Heckel, 1843.Sampling site and location were mainly in the rivers located in Khoozestan province such as Karoon and Karkheh rivers and the Dez dam. Different organs such as blood, muscle, kidney, eye and heart were sampled and analysed for the presence of tf, es, sod and pgm alleles. High polymorphism and presence of different alleles scored, but populations were not in the H-W equilibrium. Considring results, using current and avaiable genetic markers such as microsattelits is recommended for future works.
    Description: Iranian Fisheries Science Research Institute
    Description: Published
    Keywords: Chemistry ; Genetics ; Genetics Markers ; Distinguish ; Barbus ; Species ; Barbus sharpeyi ; Barbus xanthopterus ; Barbus esocinus
    Repository Name: AquaDocs
    Type: Report , Refereed
    Format: 62pp.
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  • 2
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    Trout Farms and Other Human activities Effects on Cheshmehkileh River Ecosystem in Tonekabon (2018)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    Details
    Publication Date: 2021-05-19
    Description: Cheshmehkileh River and adjacent mountainous streams, play a strategic role as a historical axis for anthropogenic civilization, human welfare also habitat and migration pathway of commercial – biologic valuable fishes e.g. Caspian trout, Caspian kuttum, members of Cyprinidae family in south Caspian Sea drainage. Treats such as overfishing of Caspian trout and Red spotted trout stocks in mountainous headwaters, barriers construction and manipulations those are out of river carrying capacity developed by human activities, affected normal function of river as well. Sand mining big factories establishment next to the river, legal and illegal trade of river sediments, direct entry of Tonekabon landfill leakage into the river, development of Rainbow trout farms since 3 decades and huge effluents into the river containing dead fish and types of solids, escapement of cultured Rainbow trouts into the river, … are major minimum factors which needs basic information for integrating inclusively drainage management system. Cheshmehkileh River contains Headwaters of Dohezar (Daryasar & Nusha), Sehezar and Valamroud rivers during 13 monthly sampling phases between September 2009 and October 2010 based on macrozoobenthoses investigations by EPT, EPT/C EPA protocols, measurements of nominated physic-chemical and microbiologic parameters. Probability of Rainbow trouts escapement and invasion, existence, nutrition in Cheshmehkileh environment indeed investigated. Data analysis explained significant differences (P〈0.05) between groups of measured parameters in different sampling stations. Dendogram of clustered analysis based on consolidation of major biologic/ physic-chemical and microbiologic parameters, separated stations No. 1, 3, 2, 4 in one group and remained classified in different groups. Station 8 and 9 similarly separated which expressed general similarities according to Sehezar river environment which were differs in comparison with other stations. Station 11 separated according to its natural quality of water and environment. Similarities between station 10 to Sehezar river stations 8 and 9 expressed general influence of Sehezar River more than Dohezar River in Cheshmehkileh condition especially in station No. 10. High scores of EPT and EPT/C indices in upstream stations 1, 3 and 8 also low score of indices in stations 7, 13 and 6 expressed levels of environment quality between these groups of stations. Maximum average biomass of macroinvertebrates belongs to Trichoptera order in Cheshmehkileh River. Significant decrease of biomass in stations 11, 12 and 13 in comparison with other stations stated environment degradation in mentioned stations relevant to excessive sand mining as well. Pollution resistant groups of invertebrates significantly increased in downstreams against upstream stations. Also disappearing of Plecoptera order in station No. 7, 9, 10 and 13 stated low quality of environment in comparison with upstream stations. Confirmation of effects quality and quantity for point and non-point sources of imported pollutants require specific management considerations in order to present exploitations, pollutants control and emergencies for river monitoring in forthcoming years.
    Description: Iranian Fisheries Science Research Institute
    Description: Published
    Keywords: River ; Pollution ; Aquaculture ; EPTC ; Assessment ; Macroinvertebrates ; Chemistry ; Microbiology
    Repository Name: AquaDocs
    Type: Report , Refereed
    Format: 138pp.
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  • 3
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    Study on effects of Beta-glucan & extraction of Sargassum & Padina algae in prevention and treatment of WSD in Fenneropenaeus indicus (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25179 | 18721 | 2018-09-03 17:23:17 | 25179 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: In this study two species of algae, Sargassum glaucescens and Padina boergeseni that found plenteously in Persian Gulf and Bushehr coast, were collected and hot water extracts of them were lyophilized. F. indicus (11.32±1.20 g), after two weeks adaptation in Shoghab research station were immersed in seawater (39 ppt and 25±1 ○C) containing hot-water extract of each brown algae, S.glaucescens and P.boergeseni, at 100, 300 and 500 mg/l concentration, Survival rate and immunological parameters (total haemocyte count (THC), total plasma protein (TPP), Phagocytic activity, bacterial clearance efficiency and bactericidal activity) were examined. In addition effect of dietary administration of beta 1, 3 1, 6 glucan on prevention of White Spot Disease and immunological parameters of shrimp were investigated. According to results, immersion in seawater containing 300 and 500 mg/l concentration of algal hot-water extract after 2 and 3 hours or oral administration of beta 1,3 1,6 glucan at level of 10 g/kg diet for 14 days significantly enhanced THC, TPP, Phagocytic activity, bacterial clearance efficiency and bactericidal activity. Immersion in seawater containing 100, 300 and 500 mg/l hot-water extract of S.glaucescens after 3 hours, improved the survival rate of WSSV-infected F. indicus.
    Keywords: Biology ; Chemistry ; Iran ; Persian Gulf ; Bushehr Province ; Beta-glucan ; Sargassum ; Padina algae ; WSD ; Fenneropenaeus indicus ; Species ; Algae ; Brown Algae ; S.glaucescens ; P.boergeseni ; Survival rate ; White Spot Disease ; Shrimp
    Repository Name: AquaDocs
    Type: monograph
    Format: application/pdf
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    Format: 57
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  • 4
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    Using biotechnology and chemical approach extraction of chitin and conversion to chitosan from the cyst shells of Artemia urmiana (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25618 | 18721 | 2018-10-07 16:34:53 | 25618 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: Chitin and chitosan are 2 very important products of biopolymer that enjoy high consumption in industry, but their production sources are very limited. In this study, Artemia urmiana cyst shells were obtained from previously collected and stored ones in Iranian Artemia Research Center. 20 kg of Artemia urmiana cyst shells were sampled, cleaned, separated, dried and transferred to Iranian Artemia Research Center Laboratory to extract their Chitin and chitosan. Their chitin and chitosan initially were extracted using optimized common chemical methods. Their properties were compared to 2 other types of Chitin and chitosan obtained from crab and shrimp manufactured by Vietnam and China, respectively. To determine their quality, elemental analysis device, infrared spectrophotometry, x –ray radiography, determination of viscosity , molecular weight, crystallinity percent, color, de stylization measure, empirical and molecular formulas were made. The results showed that the percentage of chitin obtained from Artemia cyst Shells in Chemical method was 28 ± 3 % by weight and efficiency into chitosan (grade steel relief) in this method was 50± 5%. To optimize the extraction procedure and the removal of proteins of chitin by biological practices that were done by sodium hydroxide in the chemical method, it was replaced by the bacterium Bacillus subtilis. And in the bio- phase of chitosan de steelation fungus Aspergillus niger enzyme was replaced instead of sodium hydroxide at high temperatures. The results showed that chitin and chitosan can be extracted from Artemia cyst shell using biological method and their characteristics included as in chitin 49.6% C, 8.2 % N, 7.5 % H, and 34.5 %O. Also the same levels for chitosan were 44.4 %, 8.9, 7.2 and 39.5 %, respectively. Their other quality characteristics were included chitin average molecular weight 4.9×10^6 Dalton, crystallinity percentage of 36.4, viscosity at 20°C 31 centipoise and its color was gray to brown. In the biologic method, the average molecular weight of chitosan, crystallinity percentage, viscosity at 20°C, were 5.1×105 Dalton, 94.5, and 18 centipoises, respectively. Also, its color was pale brown. Chemical structure of extracted chitin and chitosan from the shell of Artemia urmiana cysts were C_7H_12NO_4 and C_6H_11 NO_4c, respectively. The comparison of chitin and chitosan obtained from each chemical and biological method revealed that replacing biological methods instead of chemical methods is possible in achieving these products at suitable condition and better quality. This can eliminate the use of chemicals damaging the environment such as sodium hydroxide and decrease environmental pollution.
    Keywords: Biology ; Chemistry ; Iran ; Artemia urmiana cyst shell ; Chitin ; Chitosan ; Chemical ; Biological methods ; Crab shell ; Shrimp shell ; Biotechnology
    Repository Name: AquaDocs
    Type: monograph
    Format: application/pdf
    Format: application/pdf
    Format: 82
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  • 5
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    Extraction‚ purification, identification and amount verification of steroids in Sargassum glaucescens and Padina boergesni algae in Oman Sea (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25642 | 18721 | 2018-10-14 02:40:17 | 25642 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: Padina boergesenii is one of the most abundant brown algae distributed in the north of Persian Gulf and Oman Sea. In this study after sampling and preparation of Padina boergesenii by Chroform-Etanol (3-1) solvent and by Methanol has been extract. Separation and purification of the compounds was carried out using thin layer, general and inverse column chromatography, Cephadex and high-performance liquid chromatography (HPLC). Structural elucidation of the constituents was based on the data obtained from H-NMR, 13C-NMR, HSQC, HMBC, DEPT and Cephadex LH-20. The steroids compounds separated from above alga were identified as 22dehydrocholesterol (1), cholesterol (2), fucosterol (3), β-sitosterol (4), stigmasterol (5), ostreasterol (6) and two epimer of hyroxyestrol(7), based on their spectral data and from comparison with those previously reported in the literature.
    Keywords: Biology ; Chemistry ; Iran ; Oman Sea ; Persian Gulf ; Brown Algae ; Padina boergesenii ; Steroids compounds ; Extraction ; Purification ; Identification ; Amount verification ; Sargassum glaucescens ; Algae ; Abundant ; Sampling ; Chromatography ; Cephadex ; Dehydrocholesterol ; Cholesterol ; Fucosterol ; β-sitosterol ; Stigmasterol ; Ostreasterol
    Repository Name: AquaDocs
    Type: monograph
    Format: application/pdf
    Format: application/pdf
    Format: 42
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  • 6
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    Trout farms and other human activities effects on Cheshmehkileh river ecosystem in Tonekabon (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25792 | 18721 | 2018-10-13 08:54:26 | 25792 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: Cheshmehkileh River and adjacent mountainous streams, play a strategic role as a historical axis for anthropogenic civilization, human welfare also habitat and migration pathway of commercial – biologic valuable fishes e.g. Caspian trout, Caspian kuttum, members of Cyprinidae family in south Caspian Sea drainage. Treats such as overfishing of Caspian trout and Red spotted trout stocks in mountainous headwaters, barriers construction and manipulations those are out of river carrying capacity developed by human activities, affected normal function of river as well. Sand mining big factories establishment next to the river, legal and illegal trade of river sediments, direct entry of Tonekabon landfill leakage into the river, development of Rainbow trout farms since 3 decades and huge effluents into the river containing dead fish and types of solids, escapement of cultured Rainbow trouts into the river, … are major minimum factors which needs basic information for integrating inclusively drainage management system. Cheshmehkileh River contains Headwaters of Dohezar (Daryasar & Nusha), Sehezar and Valamroud rivers during 13 monthly sampling phases between September 2009 and October 2010 based on macrozoobenthoses investigations by EPT, EPT/C EPA protocols, measurements of nominated physic-chemical and microbiologic parameters. Probability of Rainbow trouts escapement and invasion, existence, nutrition in Cheshmehkileh environment indeed investigated. Data analysis explained significant differences (P〈0.05) between groups of measured parameters in different sampling stations. Dendogram of clustered analysis based on consolidation of major biologic/ physic-chemical and microbiologic parameters, separated stations No. 1, 3, 2, 4 in one group and remained classified in different groups. Station 8 and 9 similarly separated which expressed general similarities according to Sehezar river environment which were differs in comparison with other stations. Station 11 separated according to its natural quality of water and environment. Similarities between station 10 to Sehezar river stations 8 and 9 expressed general influence of Sehezar River more than Dohezar River in Cheshmehkileh condition especially in station No. 10. High scores of EPT and EPT/C indices in upstream stations 1, 3 and 8 also low score of indices in stations 7, 13 and 6 expressed levels of environment quality between these groups of stations. Maximum average biomass of macroinvertebrates belongs to Trichoptera order in Cheshmehkileh River. Significant decrease of biomass in stations 11, 12 and 13 in comparison with other stations stated environment degradation in mentioned stations relevant to excessive sand mining as well. Pollution resistant groups of invertebrates significantly increased in downstreams against upstream stations. Also disappearing of Plecoptera order in station No. 7, 9, 10 and 13 stated low quality of environment in comparison with upstream stations. Confirmation of effects quality and quantity for point and non-point sources of imported pollutants require specific management considerations in order to present exploitations, pollutants control and emergencies for river monitoring in forthcoming years.
    Keywords: Aquaculture ; Management ; Iran ; Tonekabon ; Cheshmehkileh ; River ; Pollution ; Aquaculture ; EPTC ; Assessment ; Macroinvertebrates ; Chemistry ; Microbiology
    Repository Name: AquaDocs
    Type: monograph
    Format: application/pdf
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  • 7
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    Effect of different heating treatments and kind of filling media on the amounts of some mineral elements (iron, zinc, copper, calcium and sodium) of silver carp (Hypopthalmichthys molitrix) during canning (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25429 | 18721 | 2018-09-23 16:29:13 | 25429 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: In this study, first, the influence of three precooking methods (steaming, oven-baking and microwave-cooking) on the contents of mineral elements-copper, zinc, iron, calcium and sodium-of silver carp (Hypophthalmichthys molitrix) was evaluated. Determination results of evaluated elements in raw fish and cooked samples were in range 3.05 to 4.19 for copper, 71.45 to 82.85 for zinc, 32.18 to 40.70 for iron, 425.6 to 529.46 and 315.5 to 534.76 for calcium. Results showed different precooking treatments had no significant effects on the amounts of mineral elements such as copper, zinc, calcium and sodium. The Iron content in the samples subjected to microwave cooking increased. With doing multivariate analysis, on comparing the raw and precooked fillets, steam cooking found to be the best precooking method on retain mineral elements. After choosing the best precooking method, for evaluating the influence of different filling media including sunflower oil, soybean oil, olive oil and brine, on the quality of canned silver carp, amounts of mineral elements(copper, zinc, iron, calcium and sodium) and microbial indices(total counts, thermopile count and clostridium) and sensory indices (color, smell, taste and texture) was surveyed. Assessments of microbial indices showed no microbial activity in canned products. After canning amounts of sodium increased in all the treatments. Except for iron, using soybean oil had no significant effect on the contents of other elements. The highest levels of iron and copper were observed in olive oil canned samples sterilized at 130°C. Sensory evaluating showed, kind of filling media had no significant effects on sensory indices such as taste, smell and color of canned samples. The texture of soybean oil canned samples and the quality defects of olive oil and brine canned samples had better condition than other treatments. In the last step, canned silver carp were proceed under three different temperatures (115°C, 120°C and 130°C) with equal lethality value (Fo=7min), then sensory indices and amount of mineral elements were compared. Results showed, the contents of iron, copper, sodium and calcium were changed in soybean oil canned sample. The amounts of copper and sodium in sunflower oil canned sample subjected to different heating regimes showed significant variation. The highest amount of copper was observed in the canned samples subjected to 130°C heating regime. Results showed contents of iron and copper of olive oil canned sample subjected to 120°C and 130°C heating regimes were higher than sample subjected to 115°C heating regime, while the zinc and calcium contents had no variation. In brine canned samples the highest amounts of copper and iron was obtained after sterilization in 120°C. Results of sensory evaluation showed different heating regimes had no significant effects on the indices of taste, smell, and color of products. Doing 130°C heating regime in brine canned samples led to obtain the better tenacity of texture. While this heating regime caused to increase the quality defects of soybean oil canned samples as a result of existence of hard parts of bone.
    Keywords: Chemistry ; Fisheries ; Iran ; Precooking ; Filling media ; Heating regime ; Sterilization ; Silver carp ; Mineral elements ; Hypopthalmichthys molitrix ; Samples ; Sunflower oil ; Soybean oil ; Silver Carp
    Repository Name: AquaDocs
    Type: monograph
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    Format: 109
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  • 8
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    The effect of thyroxine (T4) on prematurating in female, on survival percent, growth and development of egg and larval in rainbow trout, grass carp, silver carp and barbell of Caspian Sea (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25118 | 18721 | 2018-08-22 02:17:23 | 25118 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: Studies show that thyroxine can play an important role in regulating growth and other physiology activities. Since the direct role of thyroxine in growth metamorphose larval of bony fishes hasn't been proved yet, during the experiment accomplished in Shahid Ansari and Jajrood station, the hormones function in the survival of development of silver carp, grass carp and rainbow trout were studied. In this study accomplished of thyroxine baths with 0.1, 0.5 and 1 ppm (with 3 repeat). The other phase, thyroxine injected to females grass carp, silver carp, rainbow trout and barbell of Caspian Sea with different doses (1, 10 and 100 g/g B.W.). Tehn survival of development of embryo and larval and precent of fertilization were studied. Also, the percent of mortality were compared in two phases in stages of development. Results show that: 1) Trout: a) Phase of thyroxine bath: The number of hatching eggs and survival of larval in 0.5 ppm were increased to other treatment. b) Phase of hormone injection: The survival of larval in treatment of 10 g/g was 8.58% that was meaningful difference to other treatment (P〈0.05). 2) Silver carp: a) Phase of thyroxine bath: The number of hatching eggs and survival of larval in 0.5 ppm were (20%) increased to other treatment (P〈0.5). b) Phase of hormone injection: The survival of larval in treatment of 10 g/g was meaningful difference to other treatment (P〈0.05). 3) Grass carp: a) Phase of thyroxine bath: The number of hatching eggs and survival of larval in 0.5 ppm were 39% increased to other treatment. b) Phase of hormone injection: The survival of larval in treatment of 1 g/g was meaningful difference to other treatment (P〈0.05). 4) Barbel of Caspian Sea: Development stages wasn't determined in this fish. Number of eggs degenerated, number of eggs were the first development stages and growth of numbers increased on ovary.
    Keywords: Biology ; Chemistry ; Iran ; Caspian Sea ; Thyroxine ; Female ; Survival ; Growth ; Egg ; Larval ; Grass Carp ; Silver Carp ; Thyroxine (T4)
    Repository Name: AquaDocs
    Type: monograph
    Format: application/pdf
    Format: application/pdf
    Format: 39
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  • 9
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    Production of bio-compatible nanofiber from chitosan with electrospinning method for preservation and maintenance aquatic products (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25713 | 18721 | 2018-10-10 10:11:15 | 25713 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: Chitin nanofibers are prepared from the exoskeletons of shrimp by a simple mechanical treatment after a series of purification steps. The nanofibers have fine nanofibers networks with a uniform width of approximately 10 nm. Grinders and highpressure water jet systems are effective for disintegrating chitin into nanofibers. Acidic conditions are the key factor to facilitate mechanical fibrillation. Ultrafine fibers were successfully fabricated chitosan and fish skinextracted gelatin via electrospinning (ES). Important ES parameters, such as concentration of aqueous acid and fish gelatin solutions, and electric field intensity were examined to investigate the effects on the morphology of the gelatin nanofibers. Due to the poor mechanical properties of the fish gelatin membranes, composite nanofibers made of fish gelatin and poly(L-lactide)(PLLA) were produced with a novel solution. The introduction of PLLA remarkably improved the mechanical properties of the gelatin membranes. With a combination of good biocompatibility and mechanical properties, fish gelatin/PLGA blending non-woven mats are considered to be very promising in fish fillet coating application.. in this study, we fabricated a novel nanofibers composed of fish collagen (FC) and polycaprolactone (PCL) blends by using the electrospinning method. Nanofibers were characterized using a scanning electron microscope (SEM), and it was revealed that the diameter of nanofibers decreases as FC content was increased in the FC/PCL composite nanofibers. Several modifications to the chitin NF surface are achieved, including acetylation, deacetylation and maleylation. The results of this study revealed that: 1–It is possible to produce Nanofibers from chitosan and fish gelatin. 2– Covering and coating of processed fish by nanofibers are applicable and increasing the possibility of shell life for the processed fish. 3– Nanofibers which have been produced from chitosan and fish gelation not only is environmentally friendly but also it will be eatable while has been covered for fish fillets. biocompatible chitosan and gelatin made from fish, fresh fish fillets do not have the ability to cover and packaging, but is edible and used.
    Keywords: Biology ; Chemistry ; Fisheries ; Iran ; Chitin ; Chitosan ; Nanofiber ; Chemical modification ; Fish ; Aquatic ; Maintenance
    Repository Name: AquaDocs
    Type: monograph
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  • 10
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    Determination of sediment nutrients in the cage fish culture area (before breeding) of the southern Caspian Sea (Mazandaran coast-Kelarabad) (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25755 | 18721 | 2018-10-13 06:22:22 | 25755 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: This study was conducted to determine phosphorous and nitrogen species at the surface sediment in the southern Caspian Sea (Mazandaran Coast, Kelarabad). Surface sediments samples were collected at three stations from autumn of 2011 to winter of 2012. All samples were prepared by digesting and extracting processes and then phosphorous and nitrogen species concentrations determined using spectroscopy instrument. Results of this study showed that annual mean of Loosely-P, Fe-P, Al-P, Bioava.-P, Ca-P, TIP, Rese.-P and TP was obtained as 5.06±0.33, 55.11±2.52, 42.38±3.74, 102.52±5.68, 172.91±7.12, 275±9.12, 333.30±28.52 and 608±52 µg/g.dw, respectively. The results also showed that inorganic phophorous was less than organic phophorous during different seasons, however, mean percentage of residue-P containing organic compounds and non-degradable compounds was more than 50 percent. Percentage of Ca-P was higher than 60, whereas Bioava.-P was less than 40 percent. In addition, Fe-P and Loosely-P attained the maximum and minimum values, respectively, among the bioavailable phophorous. The order of different forms of phosphorous were recorded as Org-P〉Ca-P〉FeP〉Al-P〉Loosely-P. Annual mean of NH4/N, NO2/N, NO3/N, TIN, TON and TN were observed as 4.23±0.50, 0.06±0.01, 0.74±0.12, 5.02±0.53, 2.48±0.63 and 7.53±0.51 µg/g.dw, respectively. Annual percentage of TIN was two folds than TON and concentration of NH4/N was also four times than NO3/N. As a conclusion, the results revealed that main causes of Bioava.-P adsorption and desorption were temperature, Eh and pH. Also, the form of NH4+/N was of a high percentage because of anaerobic condition in the sediments. According to the high ratios of nitrogen/phosphorous of sediments to nitrogen and phosphorous of bottom water, it finds that released of those from the sediments to water will be happened with high rates. Therefore, it is expected that the establishment of fish farming cages should be carried out with more precautionary approaches which not leads to increased algae bloom.
    Keywords: Biology ; Chemistry ; Ecology ; Iran ; Caspian Sea ; Kelarabad ; Mazandaran coast ; Phophorous ; Nitrogen ; Surface sediment ; Determination ; Breeding
    Repository Name: AquaDocs
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  • 11
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    The feasibility commercialized study to produce vitamin and mineral premixes and binder from seaweed Sargassum ilicifolium for White leg shrimp (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25772 | 18721 | 2018-10-13 08:08:05 | 25772 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: Seaweed belonged to baseborn marine plants with cell wall containing of valued polysaccharides such as Agar, Alginate, Limen sulfate and Carmine, used as food additives and in different industries. Base on previous studies, more than 1000 MT. of Sargassum seaweed withdraw from Oman Sea in Sistan and Baluchistan coastal line which can be collect, dried and powdered for using as supplement in shrimp feed. In this project, Sargassum ilicifolium collected from 6 coastal areas, rinsed, dried, powdered and measured the nutritional values in laboratory for surveying statistically. According to the high nutritional value of Tis coastal seaweed, this variety seaweed powder, replaced with protein resources (fish meal and Soy and Wheat) of white-leg shrimp feed which was formulated by Havorash feed factory of Boshehr in four treatments (A: as control without any replacement) B: with 5%, C: 10 % and D: 15% seaweed replacement, each with three replicates in order to obtain isonitrogenus 33% CP., and iso-caloric (13% fat and 15% carbohydrate) feed using winfeed software. The weighed milled ingredients were carefully mixed using a laboratory food mixer. The mixtures were primed with 30% hot water to yield a suitable pulp. Wet diets were made into 2 mm pellet size and dried at 40 °C in a drying cabinet and maintained in standard condition which was used for water stability and absorption capacity test of the pellets in sea water, statistically one way- ANOVA. The Tis coastal seaweed with 9.8% CP, 2% lipid and 23% carbohydrate had higher nutritional value compared to the other gathered seaweed. Also amino acid and fatty acid profiles, vitamins and minerals were measured in all seaweed samples each, with three replications. As result, for using Sargassum ilicifolium as vitamins and mineral premixes in white- leg shrimp feed, Zinc, Cobalt and Phenylalanine with dose of 1.1, 06.0 and 4.0 ml. 100% dried seaweed must be added respectively. The water stability of D feed treatment in seawater (98%) and C (97%) had statistical differences with A and B (95% stability) (P〈0.05). Water absorption capacity of feeds after one hour immersion in seawater showed significance difference between D (110%) and three others, C(100%), B(85% and control(80%) (P〈0.05). As final aim of this project, enriched product of this seaweed as minerals and vitamins supplements were handsel joinery in the Second Medicine Plant Festival, 2016 and registered in recording organization to give the final certificate.
    Keywords: Aquaculture ; Chemistry ; Iran ; Sargassum illicifolium ; Sargassum illicifolium ; Mineral and vitamins supplements ; Natural binder ; Litopenaeus vannamei ; Seaweed ; Vitamin ; White leg shrimp
    Repository Name: AquaDocs
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  • 12
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    Study on the possibility of producing low-fat spread using gelatin extracted from cultured carp wastes (2021)
    Iranian Fisheries Science Research Institute | Tehran, Iran
    In:  http://aquaticcommons.org/id/eprint/25580 | 18721 | 2018-10-07 10:35:48 | 25580 | Iranian Fisheries Science Research Institute
    Details
    Publication Date: 2021-07-16
    Description: By-products consist of more than half of the total weight of fish. Most part of these wastes made from connective tissue proteins that provide good potential to produce gelatin. Nowadays, consumers are more health conscious and have responded to the call for a diet that contains low calorie and low fat. This work involved the characterization of a low-fat spread made of fish gelatin as gelling agent, emulsifier and fat replacer. Six treatments with Fish gelatin (FG) to pectin ratio 1:1 and 2:1, with pectin concentration of 1, 2 and 3%, were produced and evaluated for quality changes and storage-life at refrigerated storage. The results showed that prepared emulsions were physically stable and no phase separation observed during 8 wks. The pH of treatments was 4.5 to 4.9. The moisture content of treatments varied from 68.9% for T1 (FG/pectin ratio 1:1) to 65.4% for T6 (FG/pectin ratio 6:3). The Max. lipid of samples was measured 28.4%. Max. and min. protein of samples were 3.8% for T6 and 1.6% for T2 (FG/pectin ratio 2:1), respectively. No significant differences (p≥0.05) were observed between ash content of all treatments and control (commercial margarin). The acidity of treatments increased during storage and were significantly different from production day (p≤0.05). Peroxide value (PV) of treatments increased significantly at refrigerated storage. No significant differences were observed between PV of treatments during different wks of sampling. The results of texture profile analysis showed that firmness, compressibility and adhesiveness properties were significantly increase with higher substitution of FG with pectin. Color, Aroma, Taste and texture properties of prepared samples were found to significantly lower than control, according to sensory evaluation. Significant increases were observed in mold/yeast and psychrophilic count of treatments during storage. The macroscopic growth of molds was observed on all samples in 8th wks. No coliform growth was observed in all treatments at any time. Results suggest that low-fat spread properties were significantly influenced by different ratios of fish gelatin and pectin incorporated. It seems that these results can provide new opportunities to develop market with introducing novel products to response consumer demands. Some quality defects observed in this study can be improved by using suitable machinery at industrial scale.
    Keywords: Biology ; Chemistry ; Iran ; Fish gelatin ; Low-fat spread ; Fish wastes ; Quality characterictics ; Texture profile ; Shelf-life ; Refrigerated temperature ; Cultured Carp ; Diet ; Lipid
    Repository Name: AquaDocs
    Type: monograph
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    Format: application/pdf
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    Embryonic stem cells: don't let litigation put research off limits (2010)
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    Publication Date: 2010-09-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feng, Jian -- England -- Nature. 2010 Sep 16;467(7313):271. doi: 10.1038/467271a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20844517" target="_blank"〉PubMed〈/a〉
    Keywords: Embryo Research/economics/ethics/*legislation & jurisprudence ; *Embryonic Stem Cells ; *Federal Government ; Financing, Government/*legislation & jurisprudence ; Humans ; *Religion and Science ; Research Support as Topic/*legislation & jurisprudence ; United States ; Zygote/cytology
    Print ISSN: 0028-0836
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    Sex bias blights drug studies (2010)
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    Publication Date: 2010-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2010 Mar 18;464(7287):332-3. doi: 10.1038/464332b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237530" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bias (Epidemiology) ; Biomedical Research/*methods ; Clinical Trials as Topic/methods ; Drug Evaluation/*methods ; Female ; Humans ; Male ; Patient Selection ; Prejudice ; *Sex Characteristics ; Sex Distribution
    Print ISSN: 0028-0836
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    Human genome at ten: Life is complicated (2010)
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    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2010 Apr 1;464(7289):664-7. doi: 10.1038/464664a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360709" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Data Mining ; Gene Expression Regulation ; Genes/genetics ; Genome, Human/*genetics ; Genomics/history/trends ; History, 20th Century ; History, 21st Century ; Human Genome Project/history ; Humans ; *Models, Biological ; Molecular Biology/*history ; Neoplasms/genetics/therapy ; RNA, Untranslated/genetics/metabolism ; Sea Urchins/embryology/genetics ; Systems Biology/*trends ; Tumor Suppressor Protein p53/chemistry/genetics/metabolism ; *Uncertainty
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Calm in a crisis (2010)
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    Publication Date: 2010-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Dec 23;468(7327):1002. doi: 10.1038/4681002a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21170024" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Ecosystem ; Humans ; Information Dissemination/*methods ; Oceans and Seas ; *Science/economics/methods/trends ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Can conservation cut poverty? (2010)
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    Publication Date: 2010-09-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilbert, Natasha -- England -- Nature. 2010 Sep 16;467(7313):264-5. doi: 10.1038/467264a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20844511" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Child ; Conservation of Natural Resources/*statistics & numerical data/trends ; Hominidae ; Humans ; Malnutrition/epidemiology ; Poverty/prevention & control/*statistics & numerical data/trends ; Rivers/chemistry ; United Nations ; Water Supply/statistics & numerical data
    Print ISSN: 0028-0836
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    The genome-wide structure of the Jewish people (2010)
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    Publication Date: 2010-06-10
    Description: Contemporary Jews comprise an aggregate of ethno-religious communities whose worldwide members identify with each other through various shared religious, historical and cultural traditions. Historical evidence suggests common origins in the Middle East, followed by migrations leading to the establishment of communities of Jews in Europe, Africa and Asia, in what is termed the Jewish Diaspora. This complex demographic history imposes special challenges in attempting to address the genetic structure of the Jewish people. Although many genetic studies have shed light on Jewish origins and on diseases prevalent among Jewish communities, including studies focusing on uniparentally and biparentally inherited markers, genome-wide patterns of variation across the vast geographic span of Jewish Diaspora communities and their respective neighbours have yet to be addressed. Here we use high-density bead arrays to genotype individuals from 14 Jewish Diaspora communities and compare these patterns of genome-wide diversity with those from 69 Old World non-Jewish populations, of which 25 have not previously been reported. These samples were carefully chosen to provide comprehensive comparisons between Jewish and non-Jewish populations in the Diaspora, as well as with non-Jewish populations from the Middle East and north Africa. Principal component and structure-like analyses identify previously unrecognized genetic substructure within the Middle East. Most Jewish samples form a remarkably tight subcluster that overlies Druze and Cypriot samples but not samples from other Levantine populations or paired Diaspora host populations. In contrast, Ethiopian Jews (Beta Israel) and Indian Jews (Bene Israel and Cochini) cluster with neighbouring autochthonous populations in Ethiopia and western India, respectively, despite a clear paternal link between the Bene Israel and the Levant. These results cast light on the variegated genetic architecture of the Middle East, and trace the origins of most Jewish Diaspora communities to the Levant.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Behar, Doron M -- Yunusbayev, Bayazit -- Metspalu, Mait -- Metspalu, Ene -- Rosset, Saharon -- Parik, Juri -- Rootsi, Siiri -- Chaubey, Gyaneshwer -- Kutuev, Ildus -- Yudkovsky, Guennady -- Khusnutdinova, Elza K -- Balanovsky, Oleg -- Semino, Ornella -- Pereira, Luisa -- Comas, David -- Gurwitz, David -- Bonne-Tamir, Batsheva -- Parfitt, Tudor -- Hammer, Michael F -- Skorecki, Karl -- Villems, Richard -- England -- Nature. 2010 Jul 8;466(7303):238-42. doi: 10.1038/nature09103. Epub 2010 Jun 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Medicine Laboratory, Rambam Health Care Campus, Haifa 31096, Israel. behardm@usernet.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20531471" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Northern/ethnology ; Alleles ; Asia ; Chromosomes, Human, Y/genetics ; DNA, Mitochondrial/genetics ; Ethiopia/ethnology ; Europe ; Genome, Human/*genetics ; Genotype ; Geography ; Humans ; India/ethnology ; Jews/classification/*genetics ; Middle East/ethnology ; Phylogeny ; Principal Component Analysis
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    Smoking out the big tobacco-users - and they're not in China (2010)
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    Publication Date: 2010-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chuang, Jie-Yu -- England -- Nature. 2010 Mar 18;464(7287):350. doi: 10.1038/464350d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237541" target="_blank"〉PubMed〈/a〉
    Keywords: China/epidemiology ; Greece/epidemiology ; Humans ; Smoking/*epidemiology ; Ukraine/epidemiology
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    Technology: A flavour of the future (2010)
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    Publication Date: 2010-12-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frood, Arran -- England -- Nature. 2010 Dec 23;468(7327):S21-2. doi: 10.1038/468S21a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179082" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Technology/*trends ; Genetic Privacy/*trends ; Humans ; Internet ; *Nutrigenomics ; Nutrition Assessment ; Social Support
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    The structural basis for autonomous dimerization of the pre-T-cell antigen receptor (2010)
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    Publication Date: 2010-10-15
    Description: The pre-T-cell antigen receptor (pre-TCR), expressed by immature thymocytes, has a pivotal role in early T-cell development, including TCR beta-selection, survival and proliferation of CD4(-)CD8(-) double-negative thymocytes, and subsequent alphabeta T-cell lineage differentiation. Whereas alphabetaTCR ligation by the peptide-loaded major histocompatibility complex initiates T-cell signalling, pre-TCR-induced signalling occurs by means of a ligand-independent dimerization event. The pre-TCR comprises an invariant alpha-chain (pre-Talpha) that pairs with any TCR beta-chain (TCRbeta) following successful TCR beta-gene rearrangement. Here we provide the basis of pre-Talpha-TCRbeta assembly and pre-TCR dimerization. The pre-Talpha chain comprised a single immunoglobulin-like domain that is structurally distinct from the constant (C) domain of the TCR alpha-chain; nevertheless, the mode of association between pre-Talpha and TCRbeta mirrored that mediated by the Calpha-Cbeta domains of the alphabetaTCR. The pre-TCR had a propensity to dimerize in solution, and the molecular envelope of the pre-TCR dimer correlated well with the observed head-to-tail pre-TCR dimer. This mode of pre-TCR dimerization enabled the pre-Talpha domain to interact with the variable (V) beta domain through residues that are highly conserved across the Vbeta and joining (J) beta gene families, thus mimicking the interactions at the core of the alphabetaTCR's Valpha-Vbeta interface. Disruption of this pre-Talpha-Vbeta dimer interface abrogated pre-TCR dimerization in solution and impaired pre-TCR expression on the cell surface. Accordingly, we provide a mechanism of pre-TCR self-association that allows the pre-Talpha chain to simultaneously 'sample' the correct folding of both the V and C domains of any TCR beta-chain, regardless of its ultimate specificity, which represents a critical checkpoint in T-cell development. This unusual dual-chaperone-like sensing function of pre-Talpha represents a unique mechanism in nature whereby developmental quality control regulates the expression and signalling of an integral membrane receptor complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pang, Siew Siew -- Berry, Richard -- Chen, Zhenjun -- Kjer-Nielsen, Lars -- Perugini, Matthew A -- King, Glenn F -- Wang, Christina -- Chew, Sock Hui -- La Gruta, Nicole L -- Williams, Neal K -- Beddoe, Travis -- Tiganis, Tony -- Cowieson, Nathan P -- Godfrey, Dale I -- Purcell, Anthony W -- Wilce, Matthew C J -- McCluskey, James -- Rossjohn, Jamie -- England -- Nature. 2010 Oct 14;467(7317):844-8. doi: 10.1038/nature09448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944746" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Gene Rearrangement, T-Lymphocyte/genetics ; Humans ; Models, Molecular ; Mutation ; Protein Folding ; *Protein Multimerization ; Protein Structure, Tertiary ; Receptors, Antigen, T-Cell/*chemistry/genetics/*metabolism ; Receptors, Antigen, T-Cell, alpha-beta/chemistry/metabolism ; Signal Transduction ; Solutions ; T-Lymphocytes/cytology/immunology/metabolism
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    A long way to go (2010)
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    Publication Date: 2010-12-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Dec 2;468(7324):599-600. doi: 10.1038/468599b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124408" target="_blank"〉PubMed〈/a〉
    Keywords: Astronauts ; Humans ; International Cooperation ; Research/*economics/*trends ; Space Flight/*economics ; Spacecraft/*economics ; United States ; United States National Aeronautics and Space Administration/economics
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    Save your census (2010)
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    Publication Date: 2010-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fienberg, Stephen E -- Prewitt, Kenneth -- England -- Nature. 2010 Aug 26;466(7310):1043. doi: 10.1038/4661043a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Statistics, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213-3890, USA. fienberg@stat.cmu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20739993" target="_blank"〉PubMed〈/a〉
    Keywords: *Censuses ; *Data Collection/economics/methods/standards ; Humans
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    Which way for genetic-test regulation? Assign regulation appropriate to the level of risk (2010)
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    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Javitt, Gail -- England -- Nature. 2010 Aug 12;466(7308):817-8. doi: 10.1038/466817a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Berman Institute of Bioethics, Johns Hopkins University, USA. gjavitt1@jhu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703288" target="_blank"〉PubMed〈/a〉
    Keywords: *Consumer Advocacy ; Genetic Counseling/*legislation & jurisprudence/standards ; Genetic Predisposition to Disease/*genetics ; Genetic Testing/*legislation & jurisprudence/*standards ; *Government Regulation ; Humans ; Marketing ; Reproducibility of Results ; United States ; United States Food and Drug Administration/legislation & jurisprudence
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    Males still dominate animal studies (2010)
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    Publication Date: 2010-06-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zucker, Irving -- Beery, Annaliese K -- England -- Nature. 2010 Jun 10;465(7299):690. doi: 10.1038/465690a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departmentsof Psychology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA. irvzuck@berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535186" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bias (Epidemiology) ; Biomedical Research/ethics/*methods/trends ; *Disease Models, Animal ; Female ; Humans ; Male ; Prevalence ; *Sex Characteristics ; Sex Distribution ; Sex Factors
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    Concrete helix recalls smallpox win (2010)
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    Publication Date: 2010-11-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Licinio, Julio -- Easteal, Simon -- Wong, Ma-Li -- England -- Nature. 2010 Nov 11;468(7321):173. doi: 10.1038/468173e.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21068812" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research ; DNA, Z-Form/*chemistry ; Humans ; New South Wales ; Smallpox/*epidemiology ; Smallpox Vaccine ; Universities ; Vaccinia virus/genetics/pathogenicity
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    Stem cells: Troublesome memories (2010)
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    Publication Date: 2010-09-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zwaka, Thomas P -- England -- Nature. 2010 Sep 16;467(7313):280-1. doi: 10.1038/467280a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20844526" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/*genetics ; Cell Lineage/*genetics ; Cellular Reprogramming/genetics ; *DNA Methylation/genetics ; Embryonic Stem Cells/cytology/metabolism ; *Epigenesis, Genetic ; Humans ; Induced Pluripotent Stem Cells/*cytology/*metabolism ; Nuclear Transfer Techniques ; Organ Specificity/genetics
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    Treated fairly? (2010)
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    Publication Date: 2010-11-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Nov 25;468(7323):475-6. doi: 10.1038/468475b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21107381" target="_blank"〉PubMed〈/a〉
    Keywords: Costs and Cost Analysis/*economics/ethics/legislation & jurisprudence/trends ; Drug Costs/*legislation & jurisprudence ; Drug Industry/*economics ; Europe ; Humans
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    Foot strike patterns and collision forces in habitually barefoot versus shod runners (2010)
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    Publication Date: 2010-01-30
    Description: Humans have engaged in endurance running for millions of years, but the modern running shoe was not invented until the 1970s. For most of human evolutionary history, runners were either barefoot or wore minimal footwear such as sandals or moccasins with smaller heels and little cushioning relative to modern running shoes. We wondered how runners coped with the impact caused by the foot colliding with the ground before the invention of the modern shoe. Here we show that habitually barefoot endurance runners often land on the fore-foot (fore-foot strike) before bringing down the heel, but they sometimes land with a flat foot (mid-foot strike) or, less often, on the heel (rear-foot strike). In contrast, habitually shod runners mostly rear-foot strike, facilitated by the elevated and cushioned heel of the modern running shoe. Kinematic and kinetic analyses show that even on hard surfaces, barefoot runners who fore-foot strike generate smaller collision forces than shod rear-foot strikers. This difference results primarily from a more plantarflexed foot at landing and more ankle compliance during impact, decreasing the effective mass of the body that collides with the ground. Fore-foot- and mid-foot-strike gaits were probably more common when humans ran barefoot or in minimal shoes, and may protect the feet and lower limbs from some of the impact-related injuries now experienced by a high percentage of runners.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lieberman, Daniel E -- Venkadesan, Madhusudhan -- Werbel, William A -- Daoud, Adam I -- D'Andrea, Susan -- Davis, Irene S -- Mang'eni, Robert Ojiambo -- Pitsiladis, Yannis -- England -- Nature. 2010 Jan 28;463(7280):531-5. doi: 10.1038/nature08723.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Evolutionary Biology, 11 Divinity Avenue, Harvard University, Cambridge, Massachusetts 02138, USA. danlieb@fas.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20111000" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Biomechanical Phenomena ; Child ; Female ; Foot/*physiology ; Forefoot, Human/physiology ; Gait/physiology ; Humans ; Kenya ; Male ; Running/*physiology ; *Shoes/standards ; *Stress, Mechanical ; United States ; Weight-Bearing/physiology ; Young Adult
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    Intensive farming may ease climate change (2010)
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    Publication Date: 2010-06-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2010 Jun 17;465(7300):853. doi: 10.1038/465853a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20559354" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*methods ; Carbon/metabolism ; *Global Warming ; Humans ; Models, Theoretical ; Population Dynamics
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    Active site remodelling accompanies thioester bond formation in the SUMO E1 (2010)
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    Publication Date: 2010-02-19
    Description: E1 enzymes activate ubiquitin (Ub) and ubiquitin-like (Ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the E1 Cys domain. The structural basis for these intermediates remains unknown. Here we report crystal structures for human SUMO E1 in complex with SUMO adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 A, respectively. These structures show that side chain contacts to ATP.Mg are released after adenylation to facilitate a 130 degree rotation of the Cys domain during thioester bond formation that is accompanied by remodelling of key structural elements including the helix that contains the E1 catalytic cysteine, the crossover and re-entry loops, and refolding of two helices that are required for adenylation. These changes displace side chains required for adenylation with side chains required for thioester bond formation. Mutational and biochemical analyses indicate these mechanisms are conserved in other E1s.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866016/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olsen, Shaun K -- Capili, Allan D -- Lu, Xuequan -- Tan, Derek S -- Lima, Christopher D -- F32 GM075695/GM/NIGMS NIH HHS/ -- F32 GM075695-03/GM/NIGMS NIH HHS/ -- R01 AI068038/AI/NIAID NIH HHS/ -- R01 AI068038-02/AI/NIAID NIH HHS/ -- R01 AI068038-03/AI/NIAID NIH HHS/ -- R01 GM065872/GM/NIGMS NIH HHS/ -- R01 GM065872-09/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Feb 18;463(7283):906-12. doi: 10.1038/nature08765.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology, Sloan-Kettering Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20164921" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; *Biocatalysis ; Catalytic Domain/*physiology ; Conserved Sequence ; Crystallography, X-Ray ; Cysteine/chemistry/metabolism ; Humans ; Magnesium/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; SUMO-1 Protein/*chemistry/*metabolism ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins/metabolism ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sulfides/*metabolism ; Ubiquitin/metabolism ; Ubiquitin-Activating Enzymes/*chemistry/*metabolism ; Ubiquitins/metabolism
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    Forgotten lessons (2010)
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    Publication Date: 2010-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Basu, Paroma -- England -- Nature. 2010 Jul 15;466(7304):S14-5. doi: 10.1038/nature09241.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631697" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/drug therapy/epidemiology/prevention & ; control/psychology/transmission ; Adult ; Child ; Chronic Disease/drug therapy/epidemiology/prevention & control/psychology ; Community-Institutional Relations ; Developed Countries/*statistics & numerical data ; Female ; HIV Infections/drug therapy/*epidemiology/prevention & ; control/*psychology/transmission ; Health Education ; Humans ; Incidence ; Male ; Patient Compliance/psychology/statistics & numerical data ; Risk-Taking ; Safe Sex/*psychology/*statistics & numerical data ; Viral Load/drug effects
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    South African science: black, white and grey (2010)
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    Publication Date: 2010-02-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cherry, Michael -- England -- Nature. 2010 Feb 11;463(7282):726-8. doi: 10.1038/463726a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20148009" target="_blank"〉PubMed〈/a〉
    Keywords: Federal Government ; Humans ; Personnel Selection ; Politics ; Prejudice ; Research Personnel/economics ; Research Support as Topic/economics/organization & administration ; Science/economics/education/*manpower/*organization & administration ; South Africa
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    Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling (2010)
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    Publication Date: 2010-05-21
    Description: MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily. Here we report the crystal structure of the MyD88-IRAK4-IRAK2 death domain (DD) complex, which surprisingly reveals a left-handed helical oligomer that consists of 6 MyD88, 4 IRAK4 and 4 IRAK2 DDs. Assembly of this helical signalling tower is hierarchical, in which MyD88 recruits IRAK4 and the MyD88-IRAK4 complex recruits the IRAK4 substrates IRAK2 or the related IRAK1. Formation of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. Composite binding sites are required for recruitment of the individual DDs in the complex, which are confirmed by mutagenesis and previously identified signalling mutations. Specificities in Myddosome formation are dictated by both molecular complementarity and correspondence of surface electrostatics. The MyD88-IRAK4-IRAK2 complex provides a template for Toll signalling in Drosophila and an elegant mechanism for versatile assembly and regulation of DD complexes in signal transduction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888693/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888693/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Su-Chang -- Lo, Yu-Chih -- Wu, Hao -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI050872/AI/NIAID NIH HHS/ -- R01 AI050872-09/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Jun 17;465(7300):885-90. doi: 10.1038/nature09121. Epub 2010 May 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Weill Cornell Medical College, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485341" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; *Interleukin-1 Receptor-Associated Kinases/chemistry/metabolism ; *Models, Molecular ; *Myeloid Differentiation Factor 88/chemistry/metabolism ; Protein Structure, Tertiary ; Receptors, Interleukin-1/metabolism/*physiology ; *Signal Transduction ; Toll-Like Receptors/metabolism/*physiology
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    Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB (2010)
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    Publication Date: 2010-05-04
    Description: Polycomb group (PcG) proteins are transcriptional repressors that control processes ranging from the maintenance of cell fate decisions and stem cell pluripotency in animals to the control of flowering time in plants. In Drosophila, genetic studies identified more than 15 different PcG proteins that are required to repress homeotic (HOX) and other developmental regulator genes in cells where they must stay inactive. Biochemical analyses established that these PcG proteins exist in distinct multiprotein complexes that bind to and modify chromatin of target genes. Among those, Polycomb repressive complex 1 (PRC1) and the related dRing-associated factors (dRAF) complex contain an E3 ligase activity for monoubiquitination of histone H2A (refs 1-4). Here we show that the uncharacterized Drosophila PcG gene calypso encodes the ubiquitin carboxy-terminal hydrolase BAP1. Biochemically purified Calypso exists in a complex with the PcG protein ASX, and this complex, named Polycomb repressive deubiquitinase (PR-DUB), is bound at PcG target genes in Drosophila. Reconstituted recombinant Drosophila and human PR-DUB complexes remove monoubiquitin from H2A but not from H2B in nucleosomes. Drosophila mutants lacking PR-DUB show a strong increase in the levels of monoubiquitinated H2A. A mutation that disrupts the catalytic activity of Calypso, or absence of the ASX subunit abolishes H2A deubiquitination in vitro and HOX gene repression in vivo. Polycomb gene silencing may thus entail a dynamic balance between H2A ubiquitination by PRC1 and dRAF, and H2A deubiquitination by PR-DUB.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182123/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182123/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheuermann, Johanna C -- de Ayala Alonso, Andres Gaytan -- Oktaba, Katarzyna -- Ly-Hartig, Nga -- McGinty, Robert K -- Fraterman, Sven -- Wilm, Matthias -- Muir, Tom W -- Muller, Jurg -- R01 GM086868/GM/NIGMS NIH HHS/ -- R01 GM086868-13/GM/NIGMS NIH HHS/ -- RC2 CA148354/CA/NCI NIH HHS/ -- RC2 CA148354-02/CA/NCI NIH HHS/ -- RC2CA148354/CA/NCI NIH HHS/ -- England -- Nature. 2010 May 13;465(7295):243-7. doi: 10.1038/nature08966. Epub 2010 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20436459" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Biocatalysis ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/embryology/*enzymology/genetics/metabolism ; Gene Silencing ; Genes, Homeobox/genetics ; Genes, Insect/genetics ; Genetic Complementation Test ; Histones/*metabolism ; Humans ; Multiprotein Complexes/chemistry/isolation & purification/*metabolism ; Nucleosomes/chemistry/metabolism ; Polycomb Repressive Complex 1 ; Repressor Proteins/genetics/isolation & purification/*metabolism ; Ubiquitin/metabolism ; Ubiquitin Thiolesterase/chemistry/genetics/*metabolism ; Ubiquitination/*physiology
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    Science city chic (2010)
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    Publication Date: 2010-12-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- England -- Nature. 2010 Oct 28;467(7319):1141-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21140537" target="_blank"〉PubMed〈/a〉
    Keywords: Berlin ; Biotechnology/economics/manpower ; Career Mobility ; *Cities ; Emigration and Immigration/statistics & numerical data ; Financing, Organized ; Humans ; Public Health ; *Research Personnel/economics/statistics & numerical data/supply & distribution ; Science/economics/*manpower/*organization & administration/standards
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    Stem-cell laws in China fall short (2010)
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    Publication Date: 2010-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Oct 7;467(7316):633. doi: 10.1038/467633a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20930795" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Clinical Trials as Topic ; Evidence-Based Medicine/*legislation & jurisprudence/standards ; *Government Regulation ; Guidelines as Topic ; Humans ; Patient Advocacy/*legislation & jurisprudence/standards ; Stem Cell Transplantation/*legislation & jurisprudence/standards ; *Stem Cells
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    Regulation of myeloid leukaemia by the cell-fate determinant Musashi (2010)
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    Publication Date: 2010-07-20
    Description: Chronic myelogenous leukaemia (CML) can progress from a slow growing chronic phase to an aggressive blast crisis phase, but the molecular basis of this transition remains poorly understood. Here we have used mouse models of CML to show that disease progression is regulated by the Musashi-Numb signalling axis. Specifically, we find that the chronic phase is marked by high levels of Numb expression whereas the blast crisis phase has low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced-phase disease in vivo. As a possible explanation for the decreased levels of Numb in the blast crisis phase, we show that NUP98-HOXA9, an oncogene associated with blast crisis CML, can trigger expression of the RNA-binding protein Musashi2 (Msi2), which in turn represses Numb. Notably, loss of Msi2 restores Numb expression and significantly impairs the development and propagation of blast crisis CML in vitro and in vivo. Finally we show that Msi2 expression is not only highly upregulated during human CML progression but is also an early indicator of poorer prognosis. These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for the therapy of aggressive leukaemias.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918284/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918284/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Takahiro -- Kwon, Hyog Young -- Zimdahl, Bryan -- Congdon, Kendra L -- Blum, Jordan -- Lento, William E -- Zhao, Chen -- Lagoo, Anand -- Gerrard, Gareth -- Foroni, Letizia -- Goldman, John -- Goh, Harriet -- Kim, Soo-Hyun -- Kim, Dong-Wook -- Chuah, Charles -- Oehler, Vivian G -- Radich, Jerald P -- Jordan, Craig T -- Reya, Tannishtha -- AI067798/AI/NIAID NIH HHS/ -- CA122206/CA/NCI NIH HHS/ -- CA140371/CA/NCI NIH HHS/ -- CA18029/CA/NCI NIH HHS/ -- DK072234/DK/NIDDK NIH HHS/ -- DK63031/DK/NIDDK NIH HHS/ -- DP1 CA174422/CA/NCI NIH HHS/ -- DP1 OD006430/OD/NIH HHS/ -- DP1 OD006430-01/OD/NIH HHS/ -- DP1 OD006430-02/OD/NIH HHS/ -- DP1OD006430/OD/NIH HHS/ -- HL097767/HL/NHLBI NIH HHS/ -- P01 CA018029/CA/NCI NIH HHS/ -- R01 CA140371/CA/NCI NIH HHS/ -- R01 DK063031/DK/NIDDK NIH HHS/ -- R01 DK063031-01/DK/NIDDK NIH HHS/ -- R01 DK063031-01S1/DK/NIDDK NIH HHS/ -- R01 DK063031-02/DK/NIDDK NIH HHS/ -- R01 DK063031-03/DK/NIDDK NIH HHS/ -- R01 DK063031-04/DK/NIDDK NIH HHS/ -- R01 DK063031-05/DK/NIDDK NIH HHS/ -- R01 DK063031-06/DK/NIDDK NIH HHS/ -- R01 DK063031-07/DK/NIDDK NIH HHS/ -- R01 DK063031-07S1/DK/NIDDK NIH HHS/ -- R01 DK063031-08/DK/NIDDK NIH HHS/ -- R01 DK072234/DK/NIDDK NIH HHS/ -- R01 DK072234-01A1/DK/NIDDK NIH HHS/ -- R01 DK072234-02/DK/NIDDK NIH HHS/ -- R01 DK072234-03/DK/NIDDK NIH HHS/ -- R01 DK072234-04/DK/NIDDK NIH HHS/ -- R01 HL097767/HL/NHLBI NIH HHS/ -- R01 HL097767-01/HL/NHLBI NIH HHS/ -- R01 HL097767-02/HL/NHLBI NIH HHS/ -- T32 GM007184-33/GM/NIGMS NIH HHS/ -- U19 AI067798/AI/NIAID NIH HHS/ -- U19 AI067798-010006/AI/NIAID NIH HHS/ -- U19 AI067798-020006/AI/NIAID NIH HHS/ -- U19 AI067798-030006/AI/NIAID NIH HHS/ -- U19 AI067798-040006/AI/NIAID NIH HHS/ -- U19 AI067798-050006/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):765-8. doi: 10.1038/nature09171. Epub 2010 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20639863" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blast Crisis/genetics/metabolism/pathology ; *Cell Differentiation/genetics ; Disease Progression ; Fusion Proteins, bcr-abl/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/metabolism ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/*metabolism/*pathology ; Membrane Proteins/biosynthesis/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/biosynthesis/genetics/metabolism ; Nuclear Pore Complex Proteins/genetics/metabolism ; Oncogene Proteins, Fusion/genetics/metabolism ; Prognosis ; RNA-Binding Proteins/biosynthesis/genetics/*metabolism ; Receptor, Notch1/metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation
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    The sequencers (2010)
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    Publication Date: 2010-06-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chi, Kelly Rae -- England -- Nature. 2010 May 13;465(7295):256-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20549837" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Genome/genetics ; Genomics/economics/instrumentation/*manpower/*trends ; Humans ; Sequence Analysis, DNA/economics/instrumentation/statistics & numerical ; data/trends ; Software ; Viruses/genetics/isolation & purification
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    A systems approach (2010)
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    Publication Date: 2010-05-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chi, Kelly Rae -- England -- Nature. 2010 Apr 15;464(7291):1090-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20503480" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/genetics/metabolism/pathology/therapy ; Computational Biology/education/manpower/trends ; Female ; Genetic Heterogeneity ; Humans ; Models, Biological ; Neoplasms/genetics/*metabolism/*pathology/therapy ; Research Personnel/education ; Systems Biology/education/manpower/*trends
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    Thousands of chemical starting points for antimalarial lead identification (2010)
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    Publication Date: 2010-05-21
    Description: Malaria is a devastating infection caused by protozoa of the genus Plasmodium. Drug resistance is widespread, no new chemical class of antimalarials has been introduced into clinical practice since 1996 and there is a recent rise of parasite strains with reduced sensitivity to the newest drugs. We screened nearly 2 million compounds in GlaxoSmithKline's chemical library for inhibitors of P. falciparum, of which 13,533 were confirmed to inhibit parasite growth by at least 80% at 2 microM concentration. More than 8,000 also showed potent activity against the multidrug resistant strain Dd2. Most (82%) compounds originate from internal company projects and are new to the malaria community. Analyses using historic assay data suggest several novel mechanisms of antimalarial action, such as inhibition of protein kinases and host-pathogen interaction related targets. Chemical structures and associated data are hereby made public to encourage additional drug lead identification efforts and further research into this disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gamo, Francisco-Javier -- Sanz, Laura M -- Vidal, Jaume -- de Cozar, Cristina -- Alvarez, Emilio -- Lavandera, Jose-Luis -- Vanderwall, Dana E -- Green, Darren V S -- Kumar, Vinod -- Hasan, Samiul -- Brown, James R -- Peishoff, Catherine E -- Cardon, Lon R -- Garcia-Bustos, Jose F -- England -- Nature. 2010 May 20;465(7296):305-10. doi: 10.1038/nature09107.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485427" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimalarials/*analysis/chemistry/*pharmacology/toxicity ; Cell Line, Tumor ; *Drug Discovery ; Drug Resistance, Multiple/drug effects ; Humans ; Malaria, Falciparum/*drug therapy/parasitology ; Models, Biological ; Phylogeny ; Plasmodium falciparum/*drug effects/enzymology/genetics/growth & development ; Small Molecule Libraries/*analysis/chemistry/*pharmacology/toxicity
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    Cancer: Genomic evolution of metastasis (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-10-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luebeck, E Georg -- England -- Nature. 2010 Oct 28;467(7319):1053-5. doi: 10.1038/4671053a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981088" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Lineage/genetics ; Clone Cells/metabolism/pathology ; DNA Mutational Analysis ; Disease Progression ; Early Detection of Cancer ; *Evolution, Molecular ; Genomic Instability/*genetics ; Humans ; Models, Biological ; Mutagenesis/*genetics ; Neoplasm Metastasis/*genetics/pathology ; Pancreatic Neoplasms/classification/*genetics/*pathology ; Time Factors
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    The killing fields (2010)
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    Publication Date: 2010-09-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Sep 23;467(7314):368. doi: 10.1038/467368a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864950" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*methods ; Animals ; Cattle ; Disease Reservoirs/microbiology/*statistics & numerical data/*veterinary ; *Federal Government ; Great Britain/epidemiology ; *Mustelidae/microbiology ; Reproducibility of Results ; Tuberculosis Vaccines ; Tuberculosis, Bovine/epidemiology/*prevention & control/transmission ; Vaccination/veterinary
    Print ISSN: 0028-0836
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    A coding-independent function of gene and pseudogene mRNAs regulates tumour biology (2010)
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    Publication Date: 2010-06-26
    Description: The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206313/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206313/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poliseno, Laura -- Salmena, Leonardo -- Zhang, Jiangwen -- Carver, Brett -- Haveman, William J -- Pandolfi, Pier Paolo -- R01 CA-82328-09/CA/NCI NIH HHS/ -- R01 CA102142/CA/NCI NIH HHS/ -- R01 CA102142-07/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Jun 24;465(7301):1033-8. doi: 10.1038/nature09144.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577206" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics ; Binding, Competitive ; Cell Line ; Gene Expression Regulation, Neoplastic/*genetics ; Genes, Tumor Suppressor ; Humans ; MicroRNAs/*genetics ; Models, Genetic ; Neoplasms/*genetics ; PTEN Phosphohydrolase/*genetics ; Proto-Oncogene Proteins/genetics ; Pseudogenes/*genetics ; RNA, Messenger/*genetics ; ras Proteins/genetics
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    Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication (2010)
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    Publication Date: 2010-01-19
    Description: Influenza A virus, being responsible for seasonal epidemics and reoccurring pandemics, represents a worldwide threat to public health. High mutation rates facilitate the generation of viral escape mutants, rendering vaccines and drugs directed against virus-encoded targets potentially ineffective. In contrast, targeting host cell determinants temporarily dispensable for the host but crucial for virus replication could prevent viral escape. Here we report the discovery of 287 human host cell genes influencing influenza A virus replication in a genome-wide RNA interference (RNAi) screen. Using an independent assay we confirmed 168 hits (59%) inhibiting either the endemic H1N1 (119 hits) or the current pandemic swine-origin (121 hits) influenza A virus strains, with an overlap of 60%. Notably, a subset of these common hits was also essential for replication of a highly pathogenic avian H5N1 strain. In-depth analyses of several factors provided insights into their infection stage relevance. Notably, SON DNA binding protein (SON) was found to be important for normal trafficking of influenza virions to late endosomes early in infection. We also show that a small molecule inhibitor of CDC-like kinase 1 (CLK1) reduces influenza virus replication by more than two orders of magnitude, an effect connected with impaired splicing of the viral M2 messenger RNA. Furthermore, influenza-virus-infected p27(-/-) (cyclin-dependent kinase inhibitor 1B; Cdkn1b) mice accumulated significantly lower viral titres in the lung, providing in vivo evidence for the importance of this gene. Thus, our results highlight the potency of genome-wide RNAi screening for the dissection of virus-host interactions and the identification of drug targets for a broad range of influenza viruses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karlas, Alexander -- Machuy, Nikolaus -- Shin, Yujin -- Pleissner, Klaus-Peter -- Artarini, Anita -- Heuer, Dagmar -- Becker, Daniel -- Khalil, Hany -- Ogilvie, Lesley A -- Hess, Simone -- Maurer, Andre P -- Muller, Elke -- Wolff, Thorsten -- Rudel, Thomas -- Meyer, Thomas F -- England -- Nature. 2010 Feb 11;463(7282):818-22. doi: 10.1038/nature08760. Epub 2010 Jan 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Department, Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20081832" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Factors/genetics/metabolism ; Cell Line ; Cells, Cultured ; Chick Embryo ; Cyclin-Dependent Kinase Inhibitor p27/deficiency/genetics/metabolism ; Epithelial Cells/virology ; Genome, Human/genetics ; *Host-Pathogen Interactions/genetics/physiology ; Humans ; Influenza A Virus, H1N1 Subtype/classification/*growth & development ; Influenza, Human/*genetics/*virology ; Lung/cytology ; Mice ; Mice, Inbred C57BL ; Protein-Serine-Threonine Kinases/genetics ; Protein-Tyrosine Kinases/genetics ; *RNA Interference ; Virus Replication/*physiology
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    Origin of the human malaria parasite Plasmodium falciparum in gorillas (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-09-25
    Description: Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997044/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997044/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Weimin -- Li, Yingying -- Learn, Gerald H -- Rudicell, Rebecca S -- Robertson, Joel D -- Keele, Brandon F -- Ndjango, Jean-Bosco N -- Sanz, Crickette M -- Morgan, David B -- Locatelli, Sabrina -- Gonder, Mary K -- Kranzusch, Philip J -- Walsh, Peter D -- Delaporte, Eric -- Mpoudi-Ngole, Eitel -- Georgiev, Alexander V -- Muller, Martin N -- Shaw, George M -- Peeters, Martine -- Sharp, Paul M -- Rayner, Julian C -- Hahn, Beatrice H -- P30 AI 7767/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-21A1/AI/NIAID NIH HHS/ -- R01 AI058715/AI/NIAID NIH HHS/ -- R01 AI058715-06A1/AI/NIAID NIH HHS/ -- R01 AI058715-07/AI/NIAID NIH HHS/ -- R01 AI50529/AI/NIAID NIH HHS/ -- R01 I58715/PHS HHS/ -- R03 AI074778/AI/NIAID NIH HHS/ -- R03 AI074778-02/AI/NIAID NIH HHS/ -- R37 AI050529/AI/NIAID NIH HHS/ -- R37 AI050529-07/AI/NIAID NIH HHS/ -- R37 AI050529-08/AI/NIAID NIH HHS/ -- T32 AI007245/AI/NIAID NIH HHS/ -- T32 AI007245-26/AI/NIAID NIH HHS/ -- T32 GM008111/GM/NIGMS NIH HHS/ -- T32 GM008111-13/GM/NIGMS NIH HHS/ -- U19 AI 067854/AI/NIAID NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- U19 AI067854-06/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Sep 23;467(7314):420-5. doi: 10.1038/nature09442.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864995" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/epidemiology ; Animals ; Animals, Wild/classification/parasitology ; Ape Diseases/epidemiology/*parasitology/transmission ; DNA, Mitochondrial/analysis/genetics ; Evolution, Molecular ; Feces/parasitology ; Genes, Mitochondrial/genetics ; Genetic Variation/genetics ; Genome, Protozoan/genetics ; Gorilla gorilla/classification/*parasitology ; Humans ; Malaria, Falciparum/epidemiology/*parasitology/transmission/*veterinary ; Molecular Sequence Data ; Pan paniscus/parasitology ; Pan troglodytes/parasitology ; Phylogeny ; Plasmodium/classification/genetics/isolation & purification ; Plasmodium falciparum/genetics/*isolation & purification ; Prevalence ; Zoonoses/parasitology/transmission
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    Secrets of the shaking palsy (2010)
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    Publication Date: 2010-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnabel, Jim -- England -- Nature. 2010 Aug 26;466(7310):S2-5. doi: 10.1038/466S2b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20739933" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/metabolism ; Female ; Humans ; Male ; Mitochondria/pathology ; Neurons/*pathology ; Parkinson Disease/diagnosis/genetics/*pathology ; alpha-Synuclein/genetics/metabolism
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    Brawl in Beijing (2010)
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    Publication Date: 2010-10-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2010 Sep 30;467(7315):511. doi: 10.1038/467511a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881985" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Clinical Trials as Topic ; Homicide/*legislation & jurisprudence ; Humans ; Internet ; Research Personnel/*ethics/*legislation & jurisprudence/standards ; Scientific Misconduct ; *Truth Disclosure ; Urology/methods
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    Enzyme-inhibitor-like tuning of Ca(2+) channel connectivity with calmodulin (2010)
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    Publication Date: 2010-02-09
    Description: Ca(2+) channels and calmodulin (CaM) are two prominent signalling hubs that synergistically affect functions as diverse as cardiac excitability, synaptic plasticity and gene transcription. It is therefore fitting that these hubs are in some sense coordinated, as the opening of Ca(V)1-2 Ca(2+) channels are regulated by a single CaM constitutively complexed with channels. The Ca(2+)-free form of CaM (apoCaM) is already pre-associated with the isoleucine-glutamine (IQ) domain on the channel carboxy terminus, and subsequent Ca(2+) binding to this 'resident' CaM drives conformational changes that then trigger regulation of channel opening. Another potential avenue for channel-CaM coordination could arise from the absence of Ca(2+) regulation in channels lacking a pre-associated CaM. Natural fluctuations in CaM concentrations might then influence the fraction of regulable channels and, thereby, the overall strength of Ca(2+) feedback. However, the prevailing view has been that the ultrastrong affinity of channels for apoCaM ensures their saturation with CaM, yielding a significant form of concentration independence between Ca(2+) channels and CaM. Here we show that significant exceptions to this autonomy exist, by combining electrophysiology (to characterize channel regulation) with optical fluorescence resonance energy transfer (FRET) sensor determination of free-apoCaM concentration in live cells. This approach translates quantitative CaM biochemistry from the traditional test-tube context into the realm of functioning holochannels within intact cells. From this perspective, we find that long splice forms of Ca(V)1.3 and Ca(V)1.4 channels include a distal carboxy tail that resembles an enzyme competitive inhibitor that retunes channel affinity for apoCaM such that natural CaM variations affect the strength of Ca(2+) feedback modulation. Given the ubiquity of these channels, the connection between ambient CaM levels and Ca(2+) entry through channels is broadly significant for Ca(2+) homeostasis. Strategies such as ours promise key advances for the in situ analysis of signalling molecules resistant to in vitro reconstitution, such as Ca(2+) channels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553577/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553577/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Xiaodong -- Yang, Philemon S -- Yang, Wanjun -- Yue, David T -- P30 DC005211/DC/NIDCD NIH HHS/ -- R01 DC000276/DC/NIDCD NIH HHS/ -- England -- Nature. 2010 Feb 18;463(7283):968-72. doi: 10.1038/nature08766. Epub 2010 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Calcium Signals Laboratory, Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Ross Building, Room 713, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20139964" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Animals ; Apoproteins/analysis/metabolism ; Binding, Competitive/drug effects ; Calcium/analysis/metabolism/pharmacology ; Calcium Channel Blockers/*chemistry/*metabolism ; Calcium Channels/*chemistry/genetics/*metabolism ; Calmodulin/analysis/*metabolism ; Cell Line ; Cell Survival ; Electrophysiology ; *Feedback, Physiological ; Fluorescence Resonance Energy Transfer ; Humans ; Protein Structure, Tertiary ; Rats ; Recombinant Fusion Proteins/chemistry/genetics/metabolism
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    Protein folding: The dark side of proteins (2010)
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    Publication Date: 2010-04-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnabel, Jim -- England -- Nature. 2010 Apr 8;464(7290):828-9. doi: 10.1038/464828a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20376124" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism/pathology ; Amyloid/*biosynthesis/*chemistry/drug effects/metabolism ; Humans ; Neurodegenerative Diseases/metabolism/pathology ; Protein Denaturation/drug effects ; Protein Folding/drug effects
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    COT drives resistance to RAF inhibition through MAP kinase pathway reactivation (2010)
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    Publication Date: 2010-11-26
    Description: Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma-an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials. However, clinical responses to targeted anticancer therapeutics are frequently confounded by de novo or acquired resistance. Identification of resistance mechanisms in a manner that elucidates alternative 'druggable' targets may inform effective long-term treatment strategies. Here we expressed approximately 600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. We identified MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines. COT activates ERK primarily through MEK-dependent mechanisms that do not require RAF signalling. Moreover, COT expression is associated with de novo resistance in B-RAF(V600E) cultured cell lines and acquired resistance in melanoma cells and tissue obtained from relapsing patients following treatment with MEK or RAF inhibitors. We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058384/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058384/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johannessen, Cory M -- Boehm, Jesse S -- Kim, So Young -- Thomas, Sapana R -- Wardwell, Leslie -- Johnson, Laura A -- Emery, Caroline M -- Stransky, Nicolas -- Cogdill, Alexandria P -- Barretina, Jordi -- Caponigro, Giordano -- Hieronymus, Haley -- Murray, Ryan R -- Salehi-Ashtiani, Kourosh -- Hill, David E -- Vidal, Marc -- Zhao, Jean J -- Yang, Xiaoping -- Alkan, Ozan -- Kim, Sungjoon -- Harris, Jennifer L -- Wilson, Christopher J -- Myer, Vic E -- Finan, Peter M -- Root, David E -- Roberts, Thomas M -- Golub, Todd -- Flaherty, Keith T -- Dummer, Reinhard -- Weber, Barbara L -- Sellers, William R -- Schlegel, Robert -- Wargo, Jennifer A -- Hahn, William C -- Garraway, Levi A -- CA134502/CA/NCI NIH HHS/ -- DP2 OD002750/OD/NIH HHS/ -- DP2 OD002750-01/OD/NIH HHS/ -- K08 CA115927/CA/NCI NIH HHS/ -- K08 CA115927-05/CA/NCI NIH HHS/ -- P50 CA093683/CA/NCI NIH HHS/ -- R01 CA134502/CA/NCI NIH HHS/ -- R33 CA128625/CA/NCI NIH HHS/ -- RC2 CA148268/CA/NCI NIH HHS/ -- England -- Nature. 2010 Dec 16;468(7326):968-72. doi: 10.1038/nature09627. Epub 2010 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21107320" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Cell Line, Tumor ; Clinical Trials as Topic ; *Drug Resistance, Neoplasm/drug effects/genetics ; Enzyme Activation/drug effects ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Library ; Humans ; Indoles/pharmacology/therapeutic use ; MAP Kinase Kinase Kinases/genetics/*metabolism ; *MAP Kinase Signaling System ; Melanoma/drug therapy/enzymology/genetics/metabolism ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Open Reading Frames/genetics ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins B-raf/*antagonists & ; inhibitors/chemistry/genetics/metabolism ; Proto-Oncogene Proteins c-raf/genetics/metabolism ; Sulfonamides/pharmacology/therapeutic use
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect (2010)
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    Publication Date: 2010-04-23
    Description: The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people. Current therapy relies upon a combination of pegylated interferon-alpha and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus. The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B. Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC(50)) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log(10) reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Min -- Nettles, Richard E -- Belema, Makonen -- Snyder, Lawrence B -- Nguyen, Van N -- Fridell, Robert A -- Serrano-Wu, Michael H -- Langley, David R -- Sun, Jin-Hua -- O'Boyle, Donald R 2nd -- Lemm, Julie A -- Wang, Chunfu -- Knipe, Jay O -- Chien, Caly -- Colonno, Richard J -- Grasela, Dennis M -- Meanwell, Nicholas A -- Hamann, Lawrence G -- England -- Nature. 2010 May 6;465(7294):96-100. doi: 10.1038/nature08960. Epub 2010 Apr 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20410884" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Animals ; Antiviral Agents/blood/chemistry/*pharmacology/therapeutic use ; Cell Line ; Cercopithecus aethiops ; Drug Resistance, Viral ; Female ; Genotype ; HeLa Cells ; Hepacivirus/*drug effects ; Hepatitis C/drug therapy/virology ; Humans ; Imidazoles/blood/chemistry/*pharmacology ; Inhibitory Concentration 50 ; Male ; Middle Aged ; Time Factors ; Vero Cells ; Viral Load/drug effects ; Viral Nonstructural Proteins/*antagonists & inhibitors ; Young Adult
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Long shadow of the stem-cell ruling (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-10-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Oct 28;467(7319):1031-3. doi: 10.1038/4671031a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981069" target="_blank"〉PubMed〈/a〉
    Keywords: *Embryonic Stem Cells ; Female ; HeLa Cells ; Humans ; *Policy Making ; Politics ; Public Policy/legislation & jurisprudence/trends ; Research Personnel/economics/ethics/psychology ; Stem Cell Research/*economics/ethics/*legislation & jurisprudence ; United States
    Print ISSN: 0028-0836
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    Singular vision (2010)
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    Publication Date: 2010-05-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 May 20;465(7296):268. doi: 10.1038/465268a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485390" target="_blank"〉PubMed〈/a〉
    Keywords: Climate Change ; Europe ; European Union ; Geriatrics/trends ; Humans ; Patents as Topic ; Pensions ; Research/economics/*organization & administration/trends
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    Questioning the timeline of H1N1 flu vaccination contracts (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Deborah -- Carter, Philip -- England -- Nature. 2010 Jul 15;466(7304):315. doi: 10.1038/466315a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631779" target="_blank"〉PubMed〈/a〉
    Keywords: *Conflict of Interest ; *Drug Industry ; Humans ; *Influenza A Virus, H1N1 Subtype ; Influenza Vaccines/*supply & distribution ; Influenza, Human/*epidemiology/prevention & control/virology ; Reproducibility of Results ; Time Factors ; *Vaccination ; *World Health Organization
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    Games and play mean different things in an educational context (2010)
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    Publication Date: 2010-09-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pellegrini, Anthony D -- England -- Nature. 2010 Sep 2;467(7311):27. doi: 10.1038/467027c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20811433" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Child ; Child, Preschool ; Education ; Humans ; *Play and Playthings ; *Video Games
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    Journal club. A neuroscientist learns about algorithms for motor learning (2010)
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    Publication Date: 2010-01-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnitzer, Mark J -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jan 21;463(7279):273. doi: 10.1038/463273e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford University and Howard Hughes Medical Institute, California, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090712" target="_blank"〉PubMed〈/a〉
    Keywords: *Algorithms ; Humans ; Learning/*physiology ; Models, Neurological ; Movement/physiology ; Psychomotor Performance/*physiology ; Robotics
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    Stem cells: Cues from steroid hormones (2010)
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    Publication Date: 2010-06-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lydon, John P -- England -- Nature. 2010 Jun 10;465(7299):695-6. doi: 10.1038/465695a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535190" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/pathology ; Cell Division ; Estrogens/*metabolism ; Estrous Cycle/physiology ; Female ; Humans ; Lactation/physiology ; Mammary Glands, Animal/*cytology ; Mice ; Paracrine Communication ; Pregnancy ; Pregnancy, Animal/physiology ; Progesterone/*metabolism ; RANK Ligand/metabolism ; Receptors, Estrogen/deficiency ; Receptors, Progesterone/deficiency ; Stem Cell Niche/cytology/metabolism ; Stem Cells/*cytology/drug effects/*metabolism
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    RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF (2010)
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    Publication Date: 2010-02-25
    Description: Tumours with mutant BRAF are dependent on the RAF-MEK-ERK signalling pathway for their growth. We found that ATP-competitive RAF inhibitors inhibit ERK signalling in cells with mutant BRAF, but unexpectedly enhance signalling in cells with wild-type BRAF. Here we demonstrate the mechanistic basis for these findings. We used chemical genetic methods to show that drug-mediated transactivation of RAF dimers is responsible for paradoxical activation of the enzyme by inhibitors. Induction of ERK signalling requires direct binding of the drug to the ATP-binding site of one kinase of the dimer and is dependent on RAS activity. Drug binding to one member of RAF homodimers (CRAF-CRAF) or heterodimers (CRAF-BRAF) inhibits one protomer, but results in transactivation of the drug-free protomer. In BRAF(V600E) tumours, RAS is not activated, thus transactivation is minimal and ERK signalling is inhibited in cells exposed to RAF inhibitors. These results indicate that RAF inhibitors will be effective in tumours in which BRAF is mutated. Furthermore, because RAF inhibitors do not inhibit ERK signalling in other cells, the model predicts that they would have a higher therapeutic index and greater antitumour activity than mitogen-activated protein kinase (MEK) inhibitors, but could also cause toxicity due to MEK/ERK activation. These predictions have been borne out in a recent clinical trial of the RAF inhibitor PLX4032 (refs 4, 5). The model indicates that promotion of RAF dimerization by elevation of wild-type RAF expression or RAS activity could lead to drug resistance in mutant BRAF tumours. In agreement with this prediction, RAF inhibitors do not inhibit ERK signalling in cells that coexpress BRAF(V600E) and mutant RAS.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178447/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poulikakos, Poulikos I -- Zhang, Chao -- Bollag, Gideon -- Shokat, Kevan M -- Rosen, Neal -- 1P01CA129243-02/CA/NCI NIH HHS/ -- 2R01EB001987/EB/NIBIB NIH HHS/ -- P01 CA129243-010002/CA/NCI NIH HHS/ -- R01 EB001987/EB/NIBIB NIH HHS/ -- U01 CA091178/CA/NCI NIH HHS/ -- U01 CA091178-01/CA/NCI NIH HHS/ -- England -- Nature. 2010 Mar 18;464(7287):427-30. doi: 10.1038/nature08902.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20179705" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Catalytic Domain ; Cell Line ; Cell Line, Tumor ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Humans ; Indoles/pharmacology ; MAP Kinase Signaling System/*drug effects ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Models, Biological ; Neoplasms/drug therapy/enzymology/genetics/metabolism ; Phosphorylation ; Protein Binding ; Protein Kinase Inhibitors/metabolism/*pharmacology/therapeutic use ; Protein Multimerization ; Proto-Oncogene Proteins B-raf/antagonists & ; inhibitors/chemistry/genetics/*metabolism ; Sulfonamides/pharmacology ; Transcriptional Activation/*drug effects ; raf Kinases/*antagonists & inhibitors/chemistry/genetics/*metabolism ; ras Proteins/genetics/metabolism
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    Still prime time for primates (2010)
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    Publication Date: 2010-05-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 May 20;465(7296):267. doi: 10.1038/465267a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485389" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Rights/trends ; Animals ; Animals, Laboratory/anatomy & histology/physiology ; Cognition/*physiology ; Empathy/physiology ; Humans ; Mice ; *Models, Animal ; Neurosciences/*methods/trends ; Prefrontal Cortex/anatomy & histology/physiology ; Primates/*anatomy & histology/*physiology ; Rats
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    Good news for 'good' cholesterol (2010)
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    Publication Date: 2010-11-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsnelson, Alla -- England -- Nature. 2010 Nov 18;468(7322):354. doi: 10.1038/468354a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21085143" target="_blank"〉PubMed〈/a〉
    Keywords: C-Reactive Protein/analysis ; Cholesterol Ester Transfer Proteins/antagonists & inhibitors/metabolism ; Cholesterol, HDL/analysis/*metabolism ; Cholesterol, LDL/analysis/metabolism ; Clinical Trials as Topic ; Heart Diseases/drug therapy/prevention & control ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Oxazolidinones/adverse effects/*pharmacology/therapeutic use ; Quinolines/adverse effects ; Sulfhydryl Compounds
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    Unify guidelines for reviewing embryonic stem-cell research (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-07-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnston, Josephine -- England -- Nature. 2010 Jul 8;466(7303):179. doi: 10.1038/466179a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20613819" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Consent Forms/legislation & jurisprudence ; Embryo Research/ethics/*legislation & jurisprudence ; *Embryonic Stem Cells/cytology ; Guidelines as Topic/*standards ; Humans ; Tissue and Organ Procurement/legislation & jurisprudence
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    Cell biology: How to don a coat (2010)
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    Publication Date: 2010-06-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Traub, Linton M -- Wendland, Beverly -- R01 DK053249/DK/NIDDK NIH HHS/ -- England -- Nature. 2010 Jun 3;465(7298):556-7. doi: 10.1038/465556a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20520699" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Protein Complex 2/metabolism ; Carrier Proteins/metabolism ; Cell Membrane/*metabolism ; Clathrin-Coated Vesicles/*metabolism ; Endocytosis ; Humans ; Membrane Proteins ; Proteins/chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/metabolism
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    Literature mining: Speed reading (2010)
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    Publication Date: 2010-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lok, Corie -- England -- Nature. 2010 Jan 28;463(7280):416-8. doi: 10.1038/463416a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20110962" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bibliometrics ; Biomedical Research/*statistics & numerical data ; Data Mining/*methods ; Humans ; Online Systems ; *Periodicals as Topic
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    Immunology and the elusive AIDS vaccine (2010)
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    Publication Date: 2010-03-12
    Description: Developing a human immunodeficiency virus (HIV) vaccine is critical to end the global acquired immunodeficiency syndrome (AIDS) epidemic, but many question whether this goal is achievable. Natural immunity is not protective, and despite immunogenicity of HIV vaccine candidates, human trials have exclusively yielded disappointing results. Nevertheless, there is an indication that success may be possible, but this will be dependent on understanding the antiviral immune response in unprecedented depth to identify and engineer the types of immunity required. Here we outline fundamental immunological questions that need to be answered to develop a protective HIV vaccine, and the immediate need to harness a much broader scientific community to achieve this goal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Virgin, Herbert W -- Walker, Bruce D -- England -- Nature. 2010 Mar 11;464(7286):224-31. doi: 10.1038/nature08898.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Washington University School of Medicine and Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research, Campus Box 8118, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA. virgin@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20220841" target="_blank"〉PubMed〈/a〉
    Keywords: *AIDS Vaccines ; Acquired Immunodeficiency Syndrome/*immunology/prevention & control ; Animals ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; HIV/*immunology ; HIV Antibodies/immunology ; Humans ; Mucous Membrane/immunology
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    Systems survey of endocytosis by multiparametric image analysis (2010)
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    Publication Date: 2010-03-02
    Description: Endocytosis is a complex process fulfilling many cellular and developmental functions. Understanding how it is regulated and integrated with other cellular processes requires a comprehensive analysis of its molecular constituents and general design principles. Here, we developed a new strategy to phenotypically profile the human genome with respect to transferrin (TF) and epidermal growth factor (EGF) endocytosis by combining RNA interference, automated high-resolution confocal microscopy, quantitative multiparametric image analysis and high-performance computing. We identified several novel components of endocytic trafficking, including genes implicated in human diseases. We found that signalling pathways such as Wnt, integrin/cell adhesion, transforming growth factor (TGF)-beta and Notch regulate the endocytic system, and identified new genes involved in cargo sorting to a subset of signalling endosomes. A systems analysis by Bayesian networks further showed that the number, size, concentration of cargo and intracellular position of endosomes are not determined randomly but are subject to specific regulation, thus uncovering novel properties of the endocytic system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collinet, Claudio -- Stoter, Martin -- Bradshaw, Charles R -- Samusik, Nikolay -- Rink, Jochen C -- Kenski, Denise -- Habermann, Bianca -- Buchholz, Frank -- Henschel, Robert -- Mueller, Matthias S -- Nagel, Wolfgang E -- Fava, Eugenio -- Kalaidzidis, Yannis -- Zerial, Marino -- England -- Nature. 2010 Mar 11;464(7286):243-9. doi: 10.1038/nature08779. Epub 2010 Feb 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Molecular Cell Biology and Genetics, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20190736" target="_blank"〉PubMed〈/a〉
    Keywords: Computing Methodologies ; Endocytosis/*physiology ; Endosomes/metabolism ; Epidermal Growth Factor/metabolism ; Gene Expression Profiling/*methods ; Genome-Wide Association Study ; Humans ; *Image Processing, Computer-Assisted ; Metabolic Networks and Pathways/physiology ; Microscopy, Confocal ; Phenotype ; Protein Transport/physiology ; RNA Interference ; Signal Transduction/physiology ; Transferrin/metabolism
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    Extrinsic regulation of pluripotent stem cells (2010)
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    Publication Date: 2010-06-11
    Description: During early mammalian development, as the pluripotent cells that give rise to all of the tissues of the body proliferate and expand in number, they pass through transition states marked by a stepwise restriction in developmental potential and by changes in the expression of key regulatory genes. Recent findings show that cultured stem-cell lines derived from different stages of mouse development can mimic these transition states. They further reveal that there is a high degree of heterogeneity and plasticity in pluripotent populations in vitro and that these properties are modulated by extrinsic signalling. Understanding the extrinsic control of plasticity will guide efforts to use human pluripotent stem cells in research and therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pera, Martin F -- Tam, Patrick P L -- England -- Nature. 2010 Jun 10;465(7299):713-20. doi: 10.1038/nature09228.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. pera@usc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535200" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryonic Stem Cells/cytology/metabolism ; Humans ; Leukemia Inhibitory Factor/metabolism ; Pluripotent Stem Cells/*cytology/*physiology ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Wnt Proteins/metabolism
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    Q&A: Tod Machover on personal music. Interview by Jascha Hoffman (2010)
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    Publication Date: 2010-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Machover, Tod -- England -- Nature. 2010 Jul 15;466(7304):320. doi: 10.1038/466320a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631784" target="_blank"〉PubMed〈/a〉
    Keywords: *Drama ; Humans ; Memory ; *Music/psychology ; Music Therapy/instrumentation/methods/*trends ; Personality ; Precision Medicine/instrumentation/methods/*trends ; Robotics/*methods
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    Food: A taste of things to come? (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, Nicola -- England -- Nature. 2010 Dec 9;468(7325):752-3. doi: 10.1038/468752a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21150970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bioreactors ; Biotechnology/economics/*methods/*trends ; Chitosan/metabolism ; Conservation of Natural Resources/economics/methods/trends ; Culture Media/chemistry/economics/pharmacology ; Embryonic Stem Cells/cytology ; *Food Supply/economics ; Humans ; Meat/*supply & distribution ; *Muscles/cytology/drug effects ; Organ Culture Techniques/economics/methods/*utilization
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-08-06
    Description: Long interspersed element-1 (LINE-1 or L1) retrotransposition continues to affect human genome evolution. L1s can retrotranspose in the germline, during early development and in select somatic cells; however, the host response to L1 retrotransposition remains largely unexplored. Here we show that reporter genes introduced into the genome of various human embryonic carcinoma-derived cell lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either during or immediately after their integration. Treating ECs with histone deacetylase inhibitors rapidly reverses this silencing, and chromatin immunoprecipitation experiments revealed that reactivation of the reporter gene was correlated with changes in chromatin status at the L1 integration site. Under our assay conditions, rapid silencing was also observed when reporter genes were delivered into ECs by mouse L1s and a zebrafish LINE-2 element, but not when similar reporter genes were delivered into ECs by Moloney murine leukaemia virus or human immunodeficiency virus, suggesting that these integration events are silenced by distinct mechanisms. Finally, we demonstrate that subjecting ECs to culture conditions that promote differentiation attenuates the silencing of reporter genes delivered by L1 retrotransposition, but that differentiation, in itself, is not sufficient to reactivate previously silenced reporter genes. Thus, our data indicate that ECs differ from many differentiated cells in their ability to silence reporter genes delivered by L1 retrotransposition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034402/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034402/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia-Perez, Jose L -- Morell, Maria -- Scheys, Joshua O -- Kulpa, Deanna A -- Morell, Santiago -- Carter, Christoph C -- Hammer, Gary D -- Collins, Kathleen L -- O'Shea, K Sue -- Menendez, Pablo -- Moran, John V -- 5 P30 CA46592/CA/NCI NIH HHS/ -- GM-069985/GM/NIGMS NIH HHS/ -- GM060518/GM/NIGMS NIH HHS/ -- GM082970/GM/NIGMS NIH HHS/ -- NS-048187/NS/NINDS NIH HHS/ -- R01 DK62027/DK/NIDDK NIH HHS/ -- R01 GM060518/GM/NIGMS NIH HHS/ -- R01 GM060518-12/GM/NIGMS NIH HHS/ -- R01 GM082970/GM/NIGMS NIH HHS/ -- R01 GM082970-04/GM/NIGMS NIH HHS/ -- R01AI051198/AI/NIAID NIH HHS/ -- T32-GM08322/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 5;466(7307):769-73. doi: 10.1038/nature09209.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, 1241 East Catherine Street, University of Michigan Medical School, Ann Arbor, Michigan 48109-5618, USA. josel.garcia.perez@juntadeandalucia.es〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686575" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/genetics/physiology ; Cell Line, Tumor ; Chromatin/drug effects/genetics/metabolism ; Chromatin Immunoprecipitation ; Embryonal Carcinoma Stem Cells/*metabolism/pathology ; Epigenesis, Genetic/drug effects/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; *Gene Silencing/drug effects ; Genes, Reporter/genetics ; Genetic Engineering ; Genetic Vectors/genetics ; Genome, Human/genetics ; HIV/genetics ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Long Interspersed Nucleotide Elements/genetics ; Male ; Mice ; Models, Genetic ; Moloney murine leukemia virus/genetics ; Retroelements/*genetics ; Zebrafish/genetics
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Collateral damage (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Aug 26;466(7310):1023. doi: 10.1038/4661023a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20739963" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Periodicals as Topic ; Research Personnel/*ethics ; *Scientific Misconduct ; *Students ; United States ; United States Office of Research Integrity ; Universities/ethics
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Rule poses threat to museum bones (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Apr 1;464(7289):662. doi: 10.1038/464662a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360706" target="_blank"〉PubMed〈/a〉
    Keywords: Anthropology/*legislation & jurisprudence ; Archaeology/legislation & jurisprudence ; *Bone and Bones ; Funeral Rites ; Humans ; Indians, North American/*ethnology/legislation & jurisprudence ; *Museums ; United States
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    A new row to hoe (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Apr 1;464(7289):650. doi: 10.1038/464650a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360689" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/economics/methods/*trends ; Biofuels ; Child ; Financing, Organized/economics/trends ; Food Supply ; Global Warming/prevention & control ; Humans ; Obesity/prevention & control ; Research/economics/manpower/*trends ; Research Personnel/economics ; Research Support as Topic/economics/trends ; United States ; United States Department of Agriculture/economics/*organization & administration
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Structural basis for the suppression of skin cancers by DNA polymerase eta (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-06-26
    Description: DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030469/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030469/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Silverstein, Timothy D -- Johnson, Robert E -- Jain, Rinku -- Prakash, Louise -- Prakash, Satya -- Aggarwal, Aneel K -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 CA107650/CA/NCI NIH HHS/ -- R01 CA107650-39/CA/NCI NIH HHS/ -- R01 ES017767/ES/NIEHS NIH HHS/ -- R01 ES017767-01/ES/NIEHS NIH HHS/ -- England -- Nature. 2010 Jun 24;465(7301):1039-43. doi: 10.1038/nature09104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577207" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; DNA Damage ; DNA-Directed DNA Polymerase/*chemistry/genetics/*metabolism ; Humans ; Kinetics ; Models, Molecular ; Mutation, Missense ; Nucleic Acid Conformation ; Protein Structure, Tertiary ; Pyrimidine Dimers/chemistry/metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Skin Neoplasms/*enzymology/genetics ; Structure-Activity Relationship ; Xeroderma Pigmentosum/enzymology/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Parkinson's disease (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grayson, Michelle -- England -- Nature. 2010 Aug 26;466(7310):S1. doi: 10.1038/466S2a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20739929" target="_blank"〉PubMed〈/a〉
    Keywords: Antiparkinson Agents/therapeutic use ; Humans ; Levodopa/therapeutic use ; Parkinson Disease/*diagnosis/drug therapy/*therapy
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Temporary reprieve for stem cells (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-09-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2010 Sep 16;467(7313):258-9. doi: 10.1038/467258a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20844505" target="_blank"〉PubMed〈/a〉
    Keywords: *Embryonic Stem Cells ; Financing, Organized/economics/*organization & administration ; Humans ; Induced Pluripotent Stem Cells ; National Institutes of Health (U.S.)/*economics/*legislation & jurisprudence ; United States
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    Fossil finger points to new human species (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Mar 25;464(7288):472-3. doi: 10.1038/464472a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20336101" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA, Mitochondrial/genetics ; *Finger Phalanges ; *Fossils ; Hominidae/*classification/genetics ; Humans ; Siberia
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    Chagas disease (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-06-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grayson, Michelle -- England -- Nature. 2010 Jun 24;465(7301):S3. doi: 10.1038/465S3a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20571552" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research ; *Chagas Disease/drug therapy/epidemiology/parasitology ; Child ; Humans ; Latin America/epidemiology ; Neglected Diseases/drug therapy/epidemiology/parasitology
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    A call for collaboration (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kher, Unmesh -- England -- Nature. 2010 Jul 15;466(7304):S21-2. doi: 10.1038/nature09245.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉International AIDS Vaccine Initiative.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631702" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines ; Allergy and Immunology ; Animals ; Anti-HIV Agents/administration & dosage/supply & distribution/therapeutic use ; Biomedical Research/economics/manpower/*organization & administration/trends ; Computational Biology ; Disease Progression ; Drug Combinations ; Financing, Organized/economics ; HIV/drug effects/enzymology/genetics/isolation & purification ; HIV Infections/drug therapy/immunology/*therapy/virology ; Humans ; *Interdisciplinary Communication ; Mice ; Models, Animal ; Research Personnel/*organization & administration/trends ; Research Support as Topic/economics/organization & administration ; Systems Biology ; Treatment Outcome ; Viral Load
    Print ISSN: 0028-0836
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    Buyer beware (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Mar 25;464(7288):465-6. doi: 10.1038/464465b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20336086" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Dietary Supplements/economics/*standards ; Drug Industry/legislation & jurisprudence ; Humans ; United States
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    US stem-cell chaos felt abroad (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2010 Sep 9;467(7312):138-9. doi: 10.1038/467138a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829764" target="_blank"〉PubMed〈/a〉
    Keywords: Cooperative Behavior ; Embryo Research/*economics ; Humans ; Internationality ; Research Support as Topic/legislation & jurisprudence ; *Stem Cells ; United States
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    A land without Google? (2010)
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    Publication Date: 2010-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qiu, Jane -- England -- Nature. 2010 Feb 25;463(7284):1012-3. doi: 10.1038/4631012a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182485" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Data Collection ; *Federal Government ; Internet/legislation & jurisprudence/utilization ; *Research Personnel ; Search Engine/*legislation & jurisprudence/*utilization
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    Francis Collins: One year at the helm (2010)
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    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2010 Aug 12;466(7308):808-10. doi: 10.1038/466808a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703281" target="_blank"〉PubMed〈/a〉
    Keywords: American Recovery and Reinvestment Act/economics ; Biomedical Research/economics/organization & administration/trends ; Budgets/trends ; Comparative Effectiveness Research ; History, 20th Century ; History, 21st Century ; Human Genome Project/history ; Humans ; National Institutes of Health (U.S.)/*economics/*organization & ; administration/trends ; Religion and Science ; Translational Medical Research ; United States
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    Cancer: A wolf in wolf's clothing (2010)
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    Publication Date: 2010-05-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Green, Douglas R -- England -- Nature. 2010 May 27;465(7297):433. doi: 10.1038/465433a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20505719" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD95/deficiency/genetics/*metabolism ; Apoptosis ; Autocrine Communication ; Cell Proliferation ; Enzyme Activation ; Fas Ligand Protein/deficiency/metabolism ; Humans ; Inflammation/metabolism ; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism ; Mice ; Neoplasms/*metabolism/*pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism
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    RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-10-01
    Description: RANK ligand (RANKL), a TNF-related molecule, is essential for osteoclast formation, function and survival through interaction with its receptor RANK. Mammary glands of RANK- and RANKL-deficient mice develop normally during sexual maturation, but fail to form lobuloalveolar structures during pregnancy because of defective proliferation and increased apoptosis of mammary epithelium. It has been shown that RANKL is responsible for the major proliferative response of mouse mammary epithelium to progesterone during mammary lactational morphogenesis, and in mouse models, manipulated to induce activation of the RANK/RANKL pathway in the absence of strict hormonal control, inappropriate mammary proliferation is observed. However, there is no evidence so far of a functional contribution of RANKL to tumorigenesis. Here we show that RANK and RANKL are expressed within normal, pre-malignant and neoplastic mammary epithelium, and using complementary gain-of-function (mouse mammary tumour virus (MMTV)-RANK transgenic mice) and loss-of function (pharmacological inhibition of RANKL) approaches, define a direct contribution of this pathway in mammary tumorigenesis. Accelerated pre-neoplasias and increased mammary tumour formation were observed in MMTV-RANK transgenic mice after multiparity or treatment with carcinogen and hormone (progesterone). Reciprocally, selective pharmacological inhibition of RANKL attenuated mammary tumour development not only in hormone- and carcinogen-treated MMTV-RANK and wild-type mice, but also in the MMTV-neu transgenic spontaneous tumour model. The reduction in tumorigenesis upon RANKL inhibition was preceded by a reduction in pre-neoplasias as well as rapid and sustained reductions in hormone- and carcinogen-induced mammary epithelial proliferation and cyclin D1 levels. Collectively, our results indicate that RANKL inhibition is acting directly on hormone-induced mammary epithelium at early stages in tumorigenesis, and the permissive contribution of progesterone to increased mammary cancer incidence is due to RANKL-dependent proliferative changes in the mammary epithelium. The current study highlights a potential role for RANKL inhibition in the management of proliferative breast disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzalez-Suarez, Eva -- Jacob, Allison P -- Jones, Jon -- Miller, Robert -- Roudier-Meyer, Martine P -- Erwert, Ryan -- Pinkas, Jan -- Branstetter, Dan -- Dougall, William C -- England -- Nature. 2010 Nov 4;468(7320):103-7. doi: 10.1038/nature09495. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Hematology/Oncology Research, Amgen Inc, Seattle, Washington 98119, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881963" target="_blank"〉PubMed〈/a〉
    Keywords: 9,10-Dimethyl-1,2-benzanthracene/administration & dosage/adverse effects ; Animals ; Breast Neoplasms/metabolism/pathology ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/*chemically induced/*drug effects/pathology ; Disease Models, Animal ; Epithelial Cells/drug effects/metabolism/pathology ; Female ; Humans ; Lung Neoplasms/secondary ; Mammary Neoplasms, Experimental/*chemically ; induced/genetics/metabolism/*pathology ; Mammary Tumor Virus, Mouse/genetics/physiology ; Medroxyprogesterone Acetate/administration & dosage/adverse effects ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neoplasm Invasiveness ; Precancerous Conditions/pathology/prevention & control ; Progesterone/administration & dosage/adverse effects ; Progestins/administration & dosage/*adverse effects ; RANK Ligand/antagonists & inhibitors/genetics/*metabolism ; Receptor Activator of Nuclear Factor-kappa B/genetics/metabolism
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    Neuroscience: Editing out fear (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quirk, Gregory J -- Milad, Mohammed R -- England -- Nature. 2010 Jan 7;463(7277):36-7. doi: 10.1038/463036a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054384" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conditioning, Classical/*physiology ; Cues ; Electroshock ; Extinction, Psychological/*physiology ; Fear/*physiology/*psychology ; Humans ; Memory/*physiology ; Models, Neurological ; Models, Psychological ; Neuronal Plasticity/*physiology ; Photic Stimulation ; Rats ; Stress Disorders, Post-Traumatic/therapy ; Time Factors
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    A population-specific HTR2B stop codon predisposes to severe impulsivity (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-12-24
    Description: Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency 〉 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183507/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183507/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bevilacqua, Laura -- Doly, Stephane -- Kaprio, Jaakko -- Yuan, Qiaoping -- Tikkanen, Roope -- Paunio, Tiina -- Zhou, Zhifeng -- Wedenoja, Juho -- Maroteaux, Luc -- Diaz, Silvina -- Belmer, Arnaud -- Hodgkinson, Colin A -- Dell'osso, Liliana -- Suvisaari, Jaana -- Coccaro, Emil -- Rose, Richard J -- Peltonen, Leena -- Virkkunen, Matti -- Goldman, David -- AA-09203/AA/NIAAA NIH HHS/ -- AA-12502/AA/NIAAA NIH HHS/ -- Z01 AA000301-09/Intramural NIH HHS/ -- Z01 AA000301-10/Intramural NIH HHS/ -- Z99 AA999999/Intramural NIH HHS/ -- England -- Nature. 2010 Dec 23;468(7327):1061-6. doi: 10.1038/nature09629.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179162" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/metabolism ; Case-Control Studies ; Cell Line ; Female ; Finland ; Founder Effect ; Gene Expression Regulation ; Gene Knockout Techniques ; Genotype ; Humans ; Impulsive Behavior/*genetics ; Male ; Mental Disorders/genetics ; Mice ; Mice, 129 Strain ; Mice, Knockout ; Pedigree ; Polymorphism, Single Nucleotide/genetics ; Receptor, Serotonin, 5-HT2B/*genetics/*metabolism ; Testosterone/blood/cerebrospinal fluid
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    Love thy lab neighbour (2010)
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    Publication Date: 2010-12-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Noorden, Richard -- England -- Nature. 2010 Dec 23;468(7327):1011. doi: 10.1038/4681011a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179138" target="_blank"〉PubMed〈/a〉
    Keywords: *Bibliometrics ; *Cooperative Behavior ; Humans ; Journal Impact Factor ; Periodicals as Topic/*statistics & numerical data ; Research/*statistics & numerical data ; Universities/statistics & numerical data
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    MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake (2010)
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    Publication Date: 2010-08-10
    Description: Mitochondrial calcium uptake has a central role in cell physiology by stimulating ATP production, shaping cytosolic calcium transients and regulating cell death. The biophysical properties of mitochondrial calcium uptake have been studied in detail, but the underlying proteins remain elusive. Here we use an integrative strategy to predict human genes involved in mitochondrial calcium entry based on clues from comparative physiology, evolutionary genomics and organelle proteomics. RNA interference against 13 top candidates highlighted one gene, CBARA1, that we call hereafter mitochondrial calcium uptake 1 (MICU1). Silencing MICU1 does not disrupt mitochondrial respiration or membrane potential but abolishes mitochondrial calcium entry in intact and permeabilized cells, and attenuates the metabolic coupling between cytosolic calcium transients and activation of matrix dehydrogenases. MICU1 is associated with the mitochondrial inner membrane and has two canonical EF hands that are essential for its activity, indicating a role in calcium sensing. MICU1 represents the founding member of a set of proteins required for high-capacity mitochondrial calcium uptake. Its discovery may lead to the complete molecular characterization of mitochondrial calcium uptake pathways, and offers genetic strategies for understanding their contribution to normal physiology and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2977980/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2977980/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perocchi, Fabiana -- Gohil, Vishal M -- Girgis, Hany S -- Bao, X Robert -- McCombs, Janet E -- Palmer, Amy E -- Mootha, Vamsi K -- DK080261/DK/NIDDK NIH HHS/ -- GM0077465/GM/NIGMS NIH HHS/ -- GM084027/GM/NIGMS NIH HHS/ -- R01 GM077465/GM/NIGMS NIH HHS/ -- R01 GM077465-01A1/GM/NIGMS NIH HHS/ -- R01 GM077465-02/GM/NIGMS NIH HHS/ -- R01 GM077465-03/GM/NIGMS NIH HHS/ -- R01 GM077465-04/GM/NIGMS NIH HHS/ -- R01 GM077465-05/GM/NIGMS NIH HHS/ -- R01 GM077465-06/GM/NIGMS NIH HHS/ -- R01 GM084027/GM/NIGMS NIH HHS/ -- R24 DK080261/DK/NIDDK NIH HHS/ -- R24 DK080261-04/DK/NIDDK NIH HHS/ -- TR2 GM08759/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Sep 16;467(7313):291-6. doi: 10.1038/nature09358. Epub 2010 Aug 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20693986" target="_blank"〉PubMed〈/a〉
    Keywords: Allergens/*chemistry/genetics/*metabolism ; Amino Acid Sequence ; Antigens, Plant ; Calcium/*metabolism ; *Calcium Signaling ; Calcium-Binding Proteins/*chemistry/deficiency/genetics/*metabolism ; Cation Transport Proteins ; Cell Respiration ; Cytoplasm/metabolism ; DNA, Mitochondrial/analysis ; *EF Hand Motifs ; Endoplasmic Reticulum/metabolism ; Gene Knockdown Techniques ; HeLa Cells ; Homeostasis ; Humans ; Membrane Potentials ; Mitochondria/*metabolism ; Mitochondrial Membrane Transport Proteins ; Mitochondrial Proteins/*chemistry/deficiency/genetics/*metabolism ; NAD/metabolism ; NADP/metabolism ; Oxidative Phosphorylation ; Protein Structure, Tertiary ; Protein Transport ; RNA Interference
    Print ISSN: 0028-0836
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    Origins and functional impact of copy number variation in the human genome (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-10-09
    Description: Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Conrad, Donald F -- Pinto, Dalila -- Redon, Richard -- Feuk, Lars -- Gokcumen, Omer -- Zhang, Yujun -- Aerts, Jan -- Andrews, T Daniel -- Barnes, Chris -- Campbell, Peter -- Fitzgerald, Tomas -- Hu, Min -- Ihm, Chun Hwa -- Kristiansson, Kati -- Macarthur, Daniel G -- Macdonald, Jeffrey R -- Onyiah, Ifejinelo -- Pang, Andy Wing Chun -- Robson, Sam -- Stirrups, Kathy -- Valsesia, Armand -- Walter, Klaudia -- Wei, John -- Wellcome Trust Case Control Consortium -- Tyler-Smith, Chris -- Carter, Nigel P -- Lee, Charles -- Scherer, Stephen W -- Hurles, Matthew E -- 077006/Z/05/Z/Wellcome Trust/United Kingdom -- 077008/Wellcome Trust/United Kingdom -- 077009/Wellcome Trust/United Kingdom -- 077014/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- GM081533/GM/NIGMS NIH HHS/ -- HG004221/HG/NHGRI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Apr 1;464(7289):704-12. doi: 10.1038/nature08516. Epub 2009 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812545" target="_blank"〉PubMed〈/a〉
    Keywords: Continental Population Groups/genetics ; DNA Copy Number Variations/*genetics ; Gene Duplication ; Genetic Predisposition to Disease/*genetics ; Genome, Human/*genetics ; Genome-Wide Association Study ; Genotype ; Haplotypes/genetics ; Humans ; Mutagenesis/*genetics ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results
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    Cheap shots (2010)
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    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Aug 12;466(7308):797. doi: 10.1038/466797b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703262" target="_blank"〉PubMed〈/a〉
    Keywords: *American Recovery and Reinvestment Act/economics ; Animals ; *Dissent and Disputes ; Economic Recession ; Financing, Government/legislation & jurisprudence ; Humans ; *Politics ; Science/*economics ; United States
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    Actions speak louder than words to prevent language extinctions (2010)
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    Publication Date: 2010-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gautam, Yoshina -- Jha, Aashish -- England -- Nature. 2010 Apr 22;464(7292):1125. doi: 10.1038/4641125e.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20414287" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; *Language ; Linguistics ; Population Groups/*ethnology/*statistics & numerical data
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    Reprogramming towards pluripotency requires AID-dependent DNA demethylation (2009)
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    Publication Date: 2009-12-23
    Description: Reprogramming of somatic cell nuclei to yield induced pluripotent stem (iPS) cells makes possible derivation of patient-specific stem cells for regenerative medicine. However, iPS cell generation is asynchronous and slow (2-3 weeks), the frequency is low (〈0.1%), and DNA demethylation constitutes a bottleneck. To determine regulatory mechanisms involved in reprogramming, we generated interspecies heterokaryons (fused mouse embryonic stem (ES) cells and human fibroblasts) that induce reprogramming synchronously, frequently and fast. Here we show that reprogramming towards pluripotency in single heterokaryons is initiated without cell division or DNA replication, rapidly (1 day) and efficiently (70%). Short interfering RNA (siRNA)-mediated knockdown showed that activation-induced cytidine deaminase (AID, also known as AICDA) is required for promoter demethylation and induction of OCT4 (also known as POU5F1) and NANOG gene expression. AID protein bound silent methylated OCT4 and NANOG promoters in fibroblasts, but not active demethylated promoters in ES cells. These data provide new evidence that mammalian AID is required for active DNA demethylation and initiation of nuclear reprogramming towards pluripotency in human somatic cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906123/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906123/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhutani, Nidhi -- Brady, Jennifer J -- Damian, Mara -- Sacco, Alessandra -- Corbel, Stephane Y -- Blau, Helen M -- AG009521/AG/NIA NIH HHS/ -- AG024987/AG/NIA NIH HHS/ -- AI007328/AI/NIAID NIH HHS/ -- R01 AG009521/AG/NIA NIH HHS/ -- R01 AG009521-25/AG/NIA NIH HHS/ -- R01 AG024987/AG/NIA NIH HHS/ -- R01 AG024987-05/AG/NIA NIH HHS/ -- T32 AI007328/AI/NIAID NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1042-7. doi: 10.1038/nature08752.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory for Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5175, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20027182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Fusion ; Cell Line ; Cells, Cultured ; Cellular Reprogramming/genetics/*physiology ; Chromatin Immunoprecipitation ; Cytidine Deaminase/deficiency/genetics/*metabolism ; DNA/chemistry/genetics/metabolism ; *DNA Methylation ; DNA Replication ; Embryonic Stem Cells/cytology/metabolism ; Fibroblasts/cytology/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; Homeodomain Proteins/genetics ; Humans ; Induced Pluripotent Stem Cells/*cytology/enzymology/*metabolism ; Lung/cytology/embryology ; Mice ; Models, Biological ; Octamer Transcription Factor-3/genetics ; Promoter Regions, Genetic/genetics ; Time Factors
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    Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands (2010)
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    Publication Date: 2010-10-12
    Description: Reciprocity of inflammation, oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing and remodelling to cancer progression. Whereas the mechanism of hypoxia-driven angiogenesis is well understood, the link between inflammation-induced oxidation and de novo blood vessel growth remains obscure. Here we show that the end products of lipid oxidation, omega-(2-carboxyethyl)pyrrole (CEP) and other related pyrroles, are generated during inflammation and wound healing and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in both murine and human melanoma. The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 (TLR2), but not TLR4 or scavenger receptors on endothelial cells, leading to an angiogenic response that is independent of vascular endothelial growth factor. CEP promoted angiogenesis in hindlimb ischaemia and wound healing models through MyD88-dependent TLR2 signalling. Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue revascularization and diminished tumour angiogenesis. Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration. Taken together, these findings establish a new function of TLR2 as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990914/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990914/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉West, Xiaoxia Z -- Malinin, Nikolay L -- Merkulova, Alona A -- Tischenko, Mira -- Kerr, Bethany A -- Borden, Ernest C -- Podrez, Eugene A -- Salomon, Robert G -- Byzova, Tatiana V -- CA126847/CA/NCI NIH HHS/ -- GM021249/GM/NIGMS NIH HHS/ -- HL071625/HL/NHLBI NIH HHS/ -- HL073311/HL/NHLBI NIH HHS/ -- HL077213/HL/NHLBI NIH HHS/ -- R01 HL071625/HL/NHLBI NIH HHS/ -- R01 HL071625-07/HL/NHLBI NIH HHS/ -- R01 HL071625-08/HL/NHLBI NIH HHS/ -- R01 HL077213/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Oct 21;467(7318):972-6. doi: 10.1038/nature09421. Epub 2010 Oct 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Cardiology, J. J. Jacobs Center for Thrombosis and Vascular Biology, NB50, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927103" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism ; Animals ; Antigens, CD31/metabolism ; Aorta/cytology/drug effects ; Cell Line ; Cell Movement ; Endothelial Cells/metabolism ; Hindlimb/metabolism ; Humans ; Immunity, Innate/immunology ; Inflammation/metabolism ; Ischemia/metabolism ; Ligands ; Melanoma/blood supply/metabolism ; Mice ; Mice, Inbred C57BL ; Myeloid Differentiation Factor 88/metabolism ; Neovascularization, Pathologic/*metabolism ; *Neovascularization, Physiologic/drug effects ; Oxidation-Reduction ; Oxidative Stress/*physiology ; Propionates ; Pyrroles/chemistry/*metabolism/pharmacology ; Receptors, Scavenger/metabolism ; Signal Transduction/drug effects ; Toll-Like Receptor 2/agonists/*metabolism ; Toll-Like Receptor 4/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Wound Healing/drug effects/physiology ; rac1 GTP-Binding Protein/metabolism
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    Lawsuit rekindles gene-patent debate (2010)
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    Publication Date: 2010-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Borrell, Brendan -- England -- Nature. 2010 Jan 28;463(7280):413. doi: 10.1038/463413a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20110958" target="_blank"〉PubMed〈/a〉
    Keywords: *Genes ; Genetic Diseases, Inborn/diagnosis ; Humans ; Licensure/legislation & jurisprudence ; Molecular Diagnostic Techniques/economics ; Patents as Topic/*legislation & jurisprudence ; Universities/*legislation & jurisprudence
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    Chinese bioscience: The sequence factory (2010)
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    Publication Date: 2010-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2010 Mar 4;464(7285):22-4. doi: 10.1038/464022a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203579" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/economics/*trends ; Animals ; Breeding/economics ; China ; Genomics/economics/instrumentation/*trends ; Human Genome Project ; Humans ; Outsourced Services/economics ; Sequence Analysis, DNA/economics/instrumentation/*trends ; Workload
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    Functional genomic screen for modulators of ciliogenesis and cilium length (2010)
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    Publication Date: 2010-04-16
    Description: Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929961/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Joon -- Lee, Ji Eun -- Heynen-Genel, Susanne -- Suyama, Eigo -- Ono, Keiichiro -- Lee, Kiyoung -- Ideker, Trey -- Aza-Blanc, Pedro -- Gleeson, Joseph G -- GM070743/GM/NIGMS NIH HHS/ -- P30 CA023100/CA/NCI NIH HHS/ -- P30 CA23100/CA/NCI NIH HHS/ -- P30 NS047101/NS/NINDS NIH HHS/ -- P30 NS057096/NS/NINDS NIH HHS/ -- R01 GM070743/GM/NIGMS NIH HHS/ -- R01 NS052455/NS/NINDS NIH HHS/ -- R01 NS052455-05/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Apr 15;464(7291):1048-51. doi: 10.1038/nature08895.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosciences, Institute for Genomic Medicine, Howard Hughes Medical Institute, University of California San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393563" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Cell Line ; Cilia/drug effects/*genetics/pathology/*physiology ; Cytochalasin D/pharmacology ; Endocytosis ; Humans ; RNA Interference ; Tumor Suppressor Proteins/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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    US midterm elections: A chilly season for climate crusaders (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2010 Oct 14;467(7317):762. doi: 10.1038/467762a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944703" target="_blank"〉PubMed〈/a〉
    Keywords: Conservation of Energy Resources/legislation & jurisprudence ; Environmental Policy/*legislation & jurisprudence ; *Federal Government ; Global Warming/*legislation & jurisprudence/prevention & control ; *Politics ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Asbestos scandal (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Dec 16;468(7326):868. doi: 10.1038/468868a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164435" target="_blank"〉PubMed〈/a〉
    Keywords: Asbestos/*adverse effects/economics/*supply & distribution ; Asbestos, Serpentine/adverse effects/supply & distribution ; Carcinogens/supply & distribution/toxicity ; Construction Materials/adverse effects/economics/supply & distribution ; Humans ; Industry/economics/*legislation & jurisprudence ; Internationality ; Mesothelioma/*chemically induced/epidemiology/prevention & control
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    The evolution of eusociality (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-08-27
    Description: Eusociality, in which some individuals reduce their own lifetime reproductive potential to raise the offspring of others, underlies the most advanced forms of social organization and the ecologically dominant role of social insects and humans. For the past four decades kin selection theory, based on the concept of inclusive fitness, has been the major theoretical attempt to explain the evolution of eusociality. Here we show the limitations of this approach. We argue that standard natural selection theory in the context of precise models of population structure represents a simpler and superior approach, allows the evaluation of multiple competing hypotheses, and provides an exact framework for interpreting empirical observations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279739/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279739/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nowak, Martin A -- Tarnita, Corina E -- Wilson, Edward O -- R01 GM078986/GM/NIGMS NIH HHS/ -- R01 GM078986-04/GM/NIGMS NIH HHS/ -- R01GM078986/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Aug 26;466(7310):1057-62. doi: 10.1038/nature09205.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program for Evolutionary Dynamics, Department of Mathematics, Harvard University, Cambridge, Massachusetts 02138, USA. martin_nowak@harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20740005" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*physiology ; *Biological Evolution ; Female ; Humans ; Insects/physiology ; Male ; Models, Biological ; Selection, Genetic ; *Social Behavior
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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