Expression of nitric oxide synthase (NOS) in the developing eye of zebrafish was studied by NADPH-diaphorase staining technique. NOS activity was first observed in the optic primordium and the lens placode at 5-somite...Expression of nitric oxide synthase (NOS) in the developing eye of zebrafish was studied by NADPH-diaphorase staining technique. NOS activity was first observed in the optic primordium and the lens placode at 5-somite stage, and remained basically unchanged up to the prim-5 stage. Upon hatching, NOS activity was nearly equally detected in the gangalion cell layer and the photoreceptor layer in the developing retina. However, it began declining in the inner plexiform layer and the inner nuclear layer at this stage. NOS activity disappeared in the lens although the anterior lens epithelium was strongly stained. Two days after hatching, NOS activity was still strong in the photoreceptor layer, but decreased markedly in the gangalion cell layer, the inner plexiform layer and the inner nuclear layer with the retinal patterning. These suggested that nitric oxide (NO), the product of NOS, is not only involved in the modulation of patterning and differentiation of the retinal cells but also in the regulation of proliferation, and differentiation of the lens fibrocytes.展开更多
Human cytosolic NADP-1DH （IDH1） has recently been found to be involved in tumorigenesis. Notably, the tumorderived IDH1 mutations identified so far mainly occur at Arg132, and mutation R132H is the most prevalent on...Human cytosolic NADP-1DH （IDH1） has recently been found to be involved in tumorigenesis. Notably, the tumorderived IDH1 mutations identified so far mainly occur at Arg132, and mutation R132H is the most prevalent one. This mutation impairs the oxidative IDH activity of the enzyme, but renders a new reduction function of converting a-ketoglutarate （aKG） to 2-hydroxyglutarate. Here, we report the structures of the R132H mutant IDH1 with and without isocitrate OCT） bound. The structural data together with mutagenesis and biochemical data reveal a previ- ously undefined initial ICT-binding state and demonstrate that IDH activity requires a conformational change to a closed pre-transition state. Arg132 plays multiple functional roles in the catalytic reaction; in particular, the R132H mutation hinders the conformational changes from the initial ICT-binding state to the pre-transition state, leading to the impairment of the IDH activity. Our results describe for the first time that there is an intermediate conformation that corresponds to an initial ICT-binding state and that the R132H mutation can trap the enzyme in this conforma- tion, therefore shedding fight on the molecular mechanism of the ＂off switch＂ of the potentially tumor-suppressive IDH activity. Furthermore, we proved the necessity of Tyr139 for the gained aKG reduction activity and propose that Tyr139 may play a vital role by compensating the increased negative charge on the C2 atom of aKG during the trans- fer of a hydride anion from NADPH to aKG, which provides new insights into the mechanism of the ＂on switch＂ of the hypothetically oncogenic reduction activity of IDH1 by this mutation.展开更多
Many flaviviruses are significant human pathogens causing considerable disease burdens,including encephalitis and hemorrhagic fever,in the regions in which they are endemic.A paucity of treatments for flaviviral infec...Many flaviviruses are significant human pathogens causing considerable disease burdens,including encephalitis and hemorrhagic fever,in the regions in which they are endemic.A paucity of treatments for flaviviral infections has driven interest in drug development targeting proteins essential to flavivirus replication,such as the viral protease.During viral replication,the flavivirus genome is translated as a single polyprotein precursor,which must be cleaved into individual proteins by a complex of the viral protease,NS3,and its cofactor,NS2B.Because this cleavage is an obligate step of the viral life-cycle,the flavivirus protease is an attractive target for antiviral drug development.In this review,we will survey recent drug development studies targeting the NS3 active site,as well as studies targeting an NS2B/NS3interaction site determined from flavivirus protease crystal structures.展开更多
Entrepreneurship has become an attribute of the current growth without business activities. Entrepreneurship is a global world. It is not possible to think about economic driving force of technological development and...Entrepreneurship has become an attribute of the current growth without business activities. Entrepreneurship is a global world. It is not possible to think about economic driving force of technological development and scientific research. It materializes knowledge and involvement of people and society. Expansion of business activities is a source of individual country＇s economic performance. It contributes to the development of people＇s living standards. In every market economy, it represents an irreplaceable role for small and medium-sized enterprises （SMEs）. A strong representation of＂micro-enterprises＂ can be found in the field of personal services. Companies within the course of their existence go through particular stages of their development--from their foundation through the stage of steady development. After this stage, there comes their decline that can develop even into their termination. We indicate this process as a company life cycle. The aim of the submitted project is to map the life cycle of particularly chosen companies providing accommodation and catering services and to find a mutual relation among observed quantities and their stable economic positions in the market. The analysis is based on the data of macro-economic character, the data about development of receipts in the sector, development of inflation, tempo of economic growth, and development of consumer prices. Out of a company, non-financial factors will also be considered. The core of the analysis is the stage of sustainable stability of the assessed companies. The point of the findings is revelation of the causes of risks of possible transition into the stage of termination due to the decline of services volume, decline of profitability, and long-lasting payment insolvency. The contribution of the project is to draw our attention to possible risks of critical situation development and to propose how to avoid them so that the company will not occur in financial straits. Achieved information could assist the company management to make relevant decisions.展开更多
Agricultural market creation was critical for rural growth in Africa. How to achieve this based on crops other than major staples （e.g. maize） and traditional export crops （e.g., tea, coffee, cotton） remained a pr...Agricultural market creation was critical for rural growth in Africa. How to achieve this based on crops other than major staples （e.g. maize） and traditional export crops （e.g., tea, coffee, cotton） remained a problem since most African countries did not give them policy attention. This study used a three-tier-model, developed based on successful strategies in Nigeria and Zimbabwe, to develop multi-level soybean market creation in Kenya. Data were from secondary sources, formal and informal interviews, farm-level data, and participant observations. Analysis was carried out using Microsoft Excel and SPSS. Result showed increasing in farmers＇ confidence to produce, process, consume, and sell more soybeans than before. Trained farmers＇ groups were developing new soybean products for cash, poverty reduction and improvements in livelihoods. Net returns had been increased from 4 to 14 times from processed products. Selected farmers＇ groups had begun to supply large-scale processors with soybean grains, substituting imports. The overall project＇s impact on number of participating farmer groups and the actual land area devoted to soybean cultivation ranged from a factor of 2.3 to a factor of 77.4 between the long rainy seasons of 2005 / 2006 and the short rainy seasons of 2009. Farmers had given testimonies on live improvements.展开更多
By analyzing the information of Pingxiang Nuo masks＇ decorative patterns,this paper first briefly teases out a clue of the birth and development of historical decorative pattern and the decorative pattern category fe...By analyzing the information of Pingxiang Nuo masks＇ decorative patterns,this paper first briefly teases out a clue of the birth and development of historical decorative pattern and the decorative pattern category features of Pingxiang Nuo masks.Then, combining with the development of tourist commodities, Looking for live condition non-material cultural life rich and colorful information and spiritual practice, traditional patterns with modem visual design fusion design characteristic tourist commodities.It explores the way of how to converse the value of Pingxiang Nuo masks＇ decorative patterns into the modem design.展开更多
基金The work was supported by Ministry of Science and Technology (MOST) of China (G1999012006).
文摘Expression of nitric oxide synthase (NOS) in the developing eye of zebrafish was studied by NADPH-diaphorase staining technique. NOS activity was first observed in the optic primordium and the lens placode at 5-somite stage, and remained basically unchanged up to the prim-5 stage. Upon hatching, NOS activity was nearly equally detected in the gangalion cell layer and the photoreceptor layer in the developing retina. However, it began declining in the inner plexiform layer and the inner nuclear layer at this stage. NOS activity disappeared in the lens although the anterior lens epithelium was strongly stained. Two days after hatching, NOS activity was still strong in the photoreceptor layer, but decreased markedly in the gangalion cell layer, the inner plexiform layer and the inner nuclear layer with the retinal patterning. These suggested that nitric oxide (NO), the product of NOS, is not only involved in the modulation of patterning and differentiation of the retinal cells but also in the regulation of proliferation, and differentiation of the lens fibrocytes.
文摘Human cytosolic NADP-1DH （IDH1） has recently been found to be involved in tumorigenesis. Notably, the tumorderived IDH1 mutations identified so far mainly occur at Arg132, and mutation R132H is the most prevalent one. This mutation impairs the oxidative IDH activity of the enzyme, but renders a new reduction function of converting a-ketoglutarate （aKG） to 2-hydroxyglutarate. Here, we report the structures of the R132H mutant IDH1 with and without isocitrate OCT） bound. The structural data together with mutagenesis and biochemical data reveal a previ- ously undefined initial ICT-binding state and demonstrate that IDH activity requires a conformational change to a closed pre-transition state. Arg132 plays multiple functional roles in the catalytic reaction; in particular, the R132H mutation hinders the conformational changes from the initial ICT-binding state to the pre-transition state, leading to the impairment of the IDH activity. Our results describe for the first time that there is an intermediate conformation that corresponds to an initial ICT-binding state and that the R132H mutation can trap the enzyme in this conforma- tion, therefore shedding fight on the molecular mechanism of the ＂off switch＂ of the potentially tumor-suppressive IDH activity. Furthermore, we proved the necessity of Tyr139 for the gained aKG reduction activity and propose that Tyr139 may play a vital role by compensating the increased negative charge on the C2 atom of aKG during the trans- fer of a hydride anion from NADPH to aKG, which provides new insights into the mechanism of the ＂on switch＂ of the hypothetically oncogenic reduction activity of IDH1 by this mutation.
基金supported by grants(AI094335) from the National Institute of Health and from the Wadsworth Center Scientific Interaction Group
文摘Many flaviviruses are significant human pathogens causing considerable disease burdens,including encephalitis and hemorrhagic fever,in the regions in which they are endemic.A paucity of treatments for flaviviral infections has driven interest in drug development targeting proteins essential to flavivirus replication,such as the viral protease.During viral replication,the flavivirus genome is translated as a single polyprotein precursor,which must be cleaved into individual proteins by a complex of the viral protease,NS3,and its cofactor,NS2B.Because this cleavage is an obligate step of the viral life-cycle,the flavivirus protease is an attractive target for antiviral drug development.In this review,we will survey recent drug development studies targeting the NS3 active site,as well as studies targeting an NS2B/NS3interaction site determined from flavivirus protease crystal structures.
文摘Entrepreneurship has become an attribute of the current growth without business activities. Entrepreneurship is a global world. It is not possible to think about economic driving force of technological development and scientific research. It materializes knowledge and involvement of people and society. Expansion of business activities is a source of individual country＇s economic performance. It contributes to the development of people＇s living standards. In every market economy, it represents an irreplaceable role for small and medium-sized enterprises （SMEs）. A strong representation of＂micro-enterprises＂ can be found in the field of personal services. Companies within the course of their existence go through particular stages of their development--from their foundation through the stage of steady development. After this stage, there comes their decline that can develop even into their termination. We indicate this process as a company life cycle. The aim of the submitted project is to map the life cycle of particularly chosen companies providing accommodation and catering services and to find a mutual relation among observed quantities and their stable economic positions in the market. The analysis is based on the data of macro-economic character, the data about development of receipts in the sector, development of inflation, tempo of economic growth, and development of consumer prices. Out of a company, non-financial factors will also be considered. The core of the analysis is the stage of sustainable stability of the assessed companies. The point of the findings is revelation of the causes of risks of possible transition into the stage of termination due to the decline of services volume, decline of profitability, and long-lasting payment insolvency. The contribution of the project is to draw our attention to possible risks of critical situation development and to propose how to avoid them so that the company will not occur in financial straits. Achieved information could assist the company management to make relevant decisions.
文摘Agricultural market creation was critical for rural growth in Africa. How to achieve this based on crops other than major staples （e.g. maize） and traditional export crops （e.g., tea, coffee, cotton） remained a problem since most African countries did not give them policy attention. This study used a three-tier-model, developed based on successful strategies in Nigeria and Zimbabwe, to develop multi-level soybean market creation in Kenya. Data were from secondary sources, formal and informal interviews, farm-level data, and participant observations. Analysis was carried out using Microsoft Excel and SPSS. Result showed increasing in farmers＇ confidence to produce, process, consume, and sell more soybeans than before. Trained farmers＇ groups were developing new soybean products for cash, poverty reduction and improvements in livelihoods. Net returns had been increased from 4 to 14 times from processed products. Selected farmers＇ groups had begun to supply large-scale processors with soybean grains, substituting imports. The overall project＇s impact on number of participating farmer groups and the actual land area devoted to soybean cultivation ranged from a factor of 2.3 to a factor of 77.4 between the long rainy seasons of 2005 / 2006 and the short rainy seasons of 2009. Farmers had given testimonies on live improvements.
文摘By analyzing the information of Pingxiang Nuo masks＇ decorative patterns,this paper first briefly teases out a clue of the birth and development of historical decorative pattern and the decorative pattern category features of Pingxiang Nuo masks.Then, combining with the development of tourist commodities, Looking for live condition non-material cultural life rich and colorful information and spiritual practice, traditional patterns with modem visual design fusion design characteristic tourist commodities.It explores the way of how to converse the value of Pingxiang Nuo masks＇ decorative patterns into the modem design.
