Two Lysines in the Forkhead Domain of Foxp3 Are Key to T Regulatory Cell Function

Background: The forkhead box transcription factor, Foxp3, is master regulator of the development and function of CD4+CD25+ T regulatory (Treg) cells that limit autoimmunity and maintain immune homeostasis. The carboxyl-terminal forkhead (FKH) domain is required for the nuclear localization and DNA binding of Foxp3. We assessed how individual FKH lysines contribute to the functions of Foxp3 in Treg cells. Methodology/Principal Findings: We found that mutation of FKH lysines at position 382 (K17) and at position 393 (K18) impaired Foxp3 DNA binding and inhibited Treg suppressive function in vivo and in vitro. These lysine mutations did not affect the level of expression of Foxp3 but inhibited IL-2 promoter remodeling and had important and differing effects on Treg-associated gene expression. Conclusions/Significance: These data point to complex effects of post-translational modifications at individual lysines within the Foxp3 FKH domain that affect Treg function. Modulation of these events using small molecule inhibitors ma

Austro-Asiatic Tribes of Northeast India Provide Hitherto Missing Genetic Link between South and Southeast Asia

Northeast India, the only region which currently forms a land bridge between the Indian subcontinent and Southeast Asia, has been proposed as an important corridor for the initial peopling of East Asia. Given that the Austro-Asiatic linguistic family is considered to be the oldest and spoken by certain tribes in India, Northeast India and entire Southeast Asia, we expect that populations of this family from Northeast India should provide the signatures of genetic link between Indian and Southeast Asian populations. In order to test this hypothesis, we analyzed mtDNA and Y-Chromosome SNP and STR data of the eight groups of the Austro-Asiatic Khasi from Northeast India and the neighboring Garo and compared with that of other relevant Asian populations. The results suggest that the Austro-Asiatic Khasi tribes of Northeast India represent a genetic continuity between the populations of South and Southeast Asia, thereby advocating that northeast India could have been a major corridor for the movement of populations from India to East/Southeast Asia

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Not AvailableGenetic control of the lignification process through use of brown mid-rib (bmr) mutations has offered the most direct and productive approach to reducing lignin concentration and increasing digestibility of sorghums. Brown midrib genes were introgressed from IS 21888 (bmr-3) and IS 21891(bmr-8) into elite sorghum lines and the advanced progenies were evaluated in relation to normal sorghums. The bmr types were significantly early to flower and mature compared to normal sorghum. Normal sorghum had a significant superiority of 11 and 9% for panicle length and panicle width as compared to bmr sorghum. The bmr types recorded significantly lower grain yield than normal sorghum. However, among the bmr sorghums, CSV 15 × IS 21891 (bmr-8 mutation) derivative recorded a significant superiority over other bmr entries and was at par with the normal sorghum check CSV 20. For stover yields, normal sorghums were significantly superior to the bmr sorghums by 46%. Dry matter intake (DMI) was positively correlated with ME and IVOMD in normal sorghum. However, the correlation of DMI with IVOMD was not significant in bmr sorghums. In both the sorghums, IVOMD was positively correlated with TDN, relative feed value RFV, ME and negatively correlated with ADF and NDF. However, the association of IVOMD with NDF was non-significant in bmr sorghum. The findings of the present study indicated that bmr 3 and bmr 8 genes significantly improved the stover digestibility in specific genetic backgrounds and their interaction with recipient genetic background was evident.Not Availabl