The N-myc downstream regulated gene (Ndrg) family consists of four main members Ndrg1, 2, 3, and 4. The Ndrg genes are involved in many vital biological events including development. However, comprehensive expression patterns of this gene family during vertebrate embryogenesis remain largely unknown. Here, we analyzed the Ndrg family from the evolutionary perspective and examined the expression patterns of the Ndrg genes during Xenopus tropicalis embryogenesis. Different Ndrg family members of vertebrates are separated into different homology clusters which can be further classified into two groups and each Ndrg family member is well conserved during evolution. The temporal and spatial expression patterns of Ndrg1, 2, 3 and 4 are different during early Xenopus tropicalis development. Ndrg1, 2 and 4 are maternally expressed genes while Ndrg3 is a zygotically expressed gene. The Ndrg genes are differentially expressed in the developing central nervous system, the developing sensory organs, and the developing excretory organs. Moreover, they also show other specific expression domains. Our results indicate that the Ndrg genes exhibit specific expression patterns and may play different roles during vertebrate embryogenesis.
Background:Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor prognosis, requiring novel anticancer strategies.Methods:Mantle cell lymphoma cell lines with known p53 status were treated with GUT-70, a tricyclic coumarin derived from Calophyllum brasiliense, and the biological and biochemical consequences of GUT-70 were studied.Results:GUT-70 markedly reduced cell proliferation/viability through G1 cell cycle arrest and increased apoptosis, with greater sensitivity in mutant (mt)-p53-expressing MCL cells than in wild-type (wt)-p53-bearing cells. Mechanistically, GUT-70 showed binding affinity to heat-shock protein 90 (Hsp90) and ubiquitin-dependent proteasomal degradation of Hsp90 client proteins, including cyclin D1, Raf-1, Akt, and mt-p53. Depletion of constitutively overexpressed cyclin D1 by GUT-70 was accompanied by p27 accumulation and decreased Rb phosphorylation. GUT-70 induced mitochondrial apoptosis with Noxa upregulation and Mcl-1 downregulation in mt-p53 cells, but Mcl-1 accumulation in wt-p53 cells. Noxa and Mcl-1 were coimmunoprecipitated, and activated BAK. Treatment with a combination of GUT-70 and bortezomib or doxorubicin had synergistic antiproliferative effects in MCL cells that were independent of p53 status.Conclusion:GUT-70 has pronounced antiproliferative effects in MCL with mt-p53, a known negative prognostic factor for MCL, through Hsp90 inhibition. These findings suggest that GUT-70 has potential utility for the treatment of MCL.
This paper proposes a low cost and small size attitude and heading reference system based on MEMS inertial sensors. A dual-axis rotation structure with a proper rotary scheme according to the design principles is applied in the system to compensate for the attitude and heading drift caused by the large gyroscope biases. An optimization algorithm is applied to compensate for the installation angle error between the body frame and the rotation table's frame. Simulations and experiments are carried out to evaluate the performance of the AHRS. The results show that the proper rotation could significantly reduce the attitude and heading drifts. Moreover, the new AHRS is not affected by magnetic interference. After the rotation, the attitude and heading are almost just oscillating in a range. The attitude error is about 3° and the heading error is less than 3° which are at least 5 times better than the non-rotation condition.
In this paper, we study the alternating direction implicit (ADI) iteration for solving the continuous Sylvester equation AX + XB = C, where the coefficient matrices A and B are assumed to be positive semi‐definite matrices (not necessarily Hermitian), and at least one of them to be positive definite. We first analyze the convergence of the ADI iteration for solving such a class of Sylvester equations, then derive an upper bound for the contraction factor of this ADI iteration. To reduce its computational complexity, we further propose an inexact variant of the ADI iteration, which employs some Krylov subspace methods as its inner iteration processes at each step of the outer ADI iteration. The convergence is also analyzed in detail. The numerical experiments are given to illustrate the effectiveness of both ADI and inexact ADI iterations.
FLOWERING PROMOTING FACTOR1 (FPF1), a small protein without any known domains, promotes flowering in several plants; however, its functional mechanism remains unknown. Here, we characterized two FPF1-like proteins, FPL1 and FPL7, which, in contrast, function as flowering repressors in Brachypodium distachyon. FPL1 and FPL7 interact with the components of the florigen activation complex (FAC) and inhibit FAC activity to restrict expression of its critical target, VERNALIZATION1 (VRN1) in leaves, thereby preventing over-accumulation of FLOWERING LOCUS T1 (FT1) at the juvenile stage. Further, VRN1 can directly bind to the FPL1 promoter and repress FPL1 expression; hence, as VRN1 gradually accumulates during the late vegetative stage, FAC is released. This accurate feedback regulation of FPL1 by VRN1 allows proper FT1 expression in leaves and ensures sufficient FAC formation in shoot apical meristems to trigger timely flowering. Overall, we define a sophisticated modulatory loop for flowering initiation in a temperate grass, providing insights toward resolving the molecular basis underlying fine-tuning flowering time in plants.
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