Objective Machado-Joseph disease （MJD）, also known as spinocerebellar ataxia type 3 （SCA3）, is a dominant neurodegenerative disorder caused by an expansion of the polyglutamine （polyQ） tract in MJD-1 gene produc...Objective Machado-Joseph disease （MJD）, also known as spinocerebellar ataxia type 3 （SCA3）, is a dominant neurodegenerative disorder caused by an expansion of the polyglutamine （polyQ） tract in MJD-1 gene product, ataxin-3 （AT3）. This disease is characterized by the formation of intraneuronal inclusions, but the mechanism underlying their formation is still poorly understood. The present study is to explore the relationship between wild type （WT） AT3 and polyQ expanded AT3. Methods Mouse neuroblastoma （N2a） cells or HEK293 cells were co-transfected with WTAT3 and different truncated forms of expanded AT3. The expressions of WT AT3 and the truncated forms of expanded AT3 were detected by Western blotting, and observed by an inverted fluorescent microscope. The interactions between AT3 and different truncated forms of expanded AT3 were detected by immunoprecipitation and GST pull-down assays. Results Using fluorescent microscope, we observed that the truncated forms of expanded AT3 aggregate in transfected cells, and the full-length WT AT3 is recruited onto the aggregates. However, no aggregates were observed in cells transfected with the truncated forms of WT AT3. Immunoprecipitation and GST pull-down analyses indicate that WT AT3 interacts with the truncated AT3 in a polyQ length-dependent manner. Conclusion WT AT3 deposits in the aggregation that was formed by polyQ expanded AT3, which suggests that the formation of AT3 aggregation may affect the normal function of WT AT3 and increase polyQ protein toxicity in MJD.展开更多
This paper reports Tanzanian bankers＇ reasons for not giving SMEs the amount they request as loans to finance their businesses. Open ended interviews were used to collect primary data from eight interviews in six com...This paper reports Tanzanian bankers＇ reasons for not giving SMEs the amount they request as loans to finance their businesses. Open ended interviews were used to collect primary data from eight interviews in six commercial banks that serve SMEs and which have been in operation for more than five years. Secondary data was obtained from different documents like World Bank reports, brochures and websites of visited banks to mention the few. Findings show that sectors which are perceived as too risky by banks, poor documentation by borrowers which make banks unable to assess their creditworthiness, lack of understanding by SMEs themselves as to why they are doing businesses they do, lack or very limited knowledge on financial management by SMEs, lack of awareness of different products offered by different banks, stagnant businesses as well as lack of proper securitiries to cover their loans are reasons behind banks reluctant to provide loans to SMEs. Findings clearly show that it is still difficult for new SMEs to access finance from banks in Tanzania. It is critical for existing SMEs to put their houses in order to the level that is acceptable by banks if they need to approach banks for loans. Banks in Tanzania need to review their policies on the maximum amount of loans to SMEs to reflect the market demands. At the moment, new SMEs should not have much hope of getting finance assistance from most banks. Further, training institutions should continue educating SMEs on relevant aspect that are important to lenders and lastly, the government should consider providing guarantee to SMEs sectors that are perceived as too risky by banks just like the ongoing initiatives in the agriculture sector.展开更多
基金the National Natural Sciences Foundation of China (No.30770664)a grant from Anhui Educational Committee(No. ZD2008008-2)
文摘Objective Machado-Joseph disease （MJD）, also known as spinocerebellar ataxia type 3 （SCA3）, is a dominant neurodegenerative disorder caused by an expansion of the polyglutamine （polyQ） tract in MJD-1 gene product, ataxin-3 （AT3）. This disease is characterized by the formation of intraneuronal inclusions, but the mechanism underlying their formation is still poorly understood. The present study is to explore the relationship between wild type （WT） AT3 and polyQ expanded AT3. Methods Mouse neuroblastoma （N2a） cells or HEK293 cells were co-transfected with WTAT3 and different truncated forms of expanded AT3. The expressions of WT AT3 and the truncated forms of expanded AT3 were detected by Western blotting, and observed by an inverted fluorescent microscope. The interactions between AT3 and different truncated forms of expanded AT3 were detected by immunoprecipitation and GST pull-down assays. Results Using fluorescent microscope, we observed that the truncated forms of expanded AT3 aggregate in transfected cells, and the full-length WT AT3 is recruited onto the aggregates. However, no aggregates were observed in cells transfected with the truncated forms of WT AT3. Immunoprecipitation and GST pull-down analyses indicate that WT AT3 interacts with the truncated AT3 in a polyQ length-dependent manner. Conclusion WT AT3 deposits in the aggregation that was formed by polyQ expanded AT3, which suggests that the formation of AT3 aggregation may affect the normal function of WT AT3 and increase polyQ protein toxicity in MJD.
文摘This paper reports Tanzanian bankers＇ reasons for not giving SMEs the amount they request as loans to finance their businesses. Open ended interviews were used to collect primary data from eight interviews in six commercial banks that serve SMEs and which have been in operation for more than five years. Secondary data was obtained from different documents like World Bank reports, brochures and websites of visited banks to mention the few. Findings show that sectors which are perceived as too risky by banks, poor documentation by borrowers which make banks unable to assess their creditworthiness, lack of understanding by SMEs themselves as to why they are doing businesses they do, lack or very limited knowledge on financial management by SMEs, lack of awareness of different products offered by different banks, stagnant businesses as well as lack of proper securitiries to cover their loans are reasons behind banks reluctant to provide loans to SMEs. Findings clearly show that it is still difficult for new SMEs to access finance from banks in Tanzania. It is critical for existing SMEs to put their houses in order to the level that is acceptable by banks if they need to approach banks for loans. Banks in Tanzania need to review their policies on the maximum amount of loans to SMEs to reflect the market demands. At the moment, new SMEs should not have much hope of getting finance assistance from most banks. Further, training institutions should continue educating SMEs on relevant aspect that are important to lenders and lastly, the government should consider providing guarantee to SMEs sectors that are perceived as too risky by banks just like the ongoing initiatives in the agriculture sector.
