Reduction of Mitoferrin Results in Abnormal Development and Extended Lifespan in Caenorhabditis elegans

Iron is essential for organisms. It is mainly utilized in mitochondria for biosynthesis of iron-sulfur clusters, hemes and other cofactors. Mitoferrin 1 and mitoferrin 2, two homologues proteins belonging to the mitochondrial solute carrier family, are required for iron delivery into mitochondria. Mitoferrin 1 is highly expressed in developing erythrocytes which consume a large amount of iron during hemoglobinization. Mitoferrin 2 is ubiquitously expressed, whose functions are less known. Zebrafish with mitoferrin 1 mutation show profound hypochromic anaemia and erythroid maturation arrests, and yeast with defects in MRS3/4, the counterparts of mitoferrin 1/2, has low mitochondrial iron levels and grows poorly by iron depletion. Mitoferrin 1 expression is up-regulated in yeast and mouse models of Fiedreich's ataxia disease and in human cell culture models of Parkinson disease, suggesting its involvement in the pathogenesis of diseases with mitochondrial iron accumulation. In this study we found that reduced mitoferrin levels in C. elegans by RNAi treatment causes pleiotropic phenotypes such as small body size, reduced fecundity, slow movement and increased sensitivity to paraquat. Despite these abnormities, lifespan was increased by 50% to 80% in N2 wild type strain, and in further studies using the RNAi sensitive strain eri-1, more than doubled lifespan was observed. The pathways or mechanisms responsible for the lifespan extension and other phenotypes of mitoferrin RNAi worms are worth further study, which may contribute to our understanding of aging mechanisms and the pathogenesis of iron disorder related diseases

Multilevel augmentation algorithms based on fast collocation methods for solving ill-posed integral equations

AbstractThis paper continues the theme of the recent work Chen et al. (2008) [18], in which fast collocation methods are introduced for solving ill-posed Fredholm integral equations of the first kind. We develop in this paper multilevel augmentation algorithms, which lead to fast solutions of the discrete equations resulting from fast collocation methods. Regularization parameter choice strategies are given for proposed methods. The theoretical analysis and numerical experiments illustrate the accuracy and efficiency of the algorithm

Temporal expression of Pelp1 during proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells.

BACKGROUND: Osteogenic induction and bone formation are heavily affected by environmental factors, including estrogen, estrogen receptors, and coregulatory proteins, such as the recently reported proline-, glutamic acid-, and leucine-rich protein 1(Pelp1). OBJECTIVE: To investigate Pelp1 expression in rat bone mesenchymal stem cells (rBMSCs) during cell proliferation and osteogenic differentiation. METHODS: rBMSCs were cultured in routine and osteogenic differentiation media. Cell proliferation was assessed at days 1, 3, 5, 7, 9, 11, 14, and 21. Pelp1 protein expression in the nucleus and cytoplasm were detected by immunocytochemical analysis. Real-time RT-PCR and western blot were used to detect mRNA and protein expressions of Pelp1, osteocalcin (OCN), and alkaline phosphatase (ALP). RESULTS: Over 21 days, rBMSCs in routine culture exhibited a 1-2 day lag phase and exponential growth from day 3 to 9, plateauing at day 9, and correlated with temporal mRNA expression of Pelp1, which almost reached baseline levels at day 21. In osteogenic induction cultures, Pelp1 mRNA levels rose at day 9 and steadily increased until day 21, reaching 6.8-fold greater value compared with day 1. Interestingly, Pelp1 mRNA expression in osteogenic cultures exhibited a trend similar to that of OCN expression. Pelp1 knockdown by siRNA transfection inhibited undifferentiated rBMSC proliferation, and bone markers OCN and ALP expressions in rBMSCs cultured in routine and osteogenic differentiation media. CONCLUSIONS: Pelp1 may be a key player in BMSCs proliferation and osteogenic differentiation, meriting further consideration as a target for development of therapies for pathological bone loss conditions, such as menopausal bone loss

Side‐Gate BN‐MoS2 Transistor for Reconfigurable Multifunctional Electronics

Abstract Developing 2D reconfigurable multifunctional devices is of great potential in further miniaturizing the chip area and simplifying circuit design. 2D van der Waals (vdW) heterostructures offer a novel approach to realizing reconfigurable multifunctional devices. Despite the numerous previous reports that have integrated various functions in a single 2D heterostructures device, most of those devices are based on a complex multilayer heterostructure or an air‐unstable channel material, limiting their ability to be applied in integrated circuits. There is an urgent need to develop 2D reconfigurable multifunctional devices that have a simple structure and stable electrical properties. In this work, a side‐gate reconfigurable device is illustrated based on simple BN‐MoS2 vdW heterostructures. Three different functions in a single device have been achieved, including a diode, double‐side‐gate reconfigurable logic transistor, and top floating gate memory. A lateral n+‐n homojunction is created along the MoS2 channel and the rectification ratio is above 105. Reconfigurable logic operations (OR, AND) can be achieved in a single double‐side‐gate device and the current on/off ratio is ≈t 104. Moreover, the device can act as a floating gate memory under back gate operation. Those results pave the way for integrating the same reconfigurable multifunctional devices to realize complex electronic systems