DIA-Based Proteomics Identifies IDH2 as a Targetable Regulator of Acquired Drug Resistance in Chronic Myeloid Leukemia

Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR.     

The Optimal Solution of a Non-Convex State-Dependent LQR Problem and Its Applications

This paper studies a Non-convex State-dependent Linear Quadratic Regulator (NSLQR) problem, in which the control penalty weighting matrix in the performance index is state-dependent. A necessary and sufficient condition for the optimal solution is established with a rigorous proof by Euler-Lagrange Equation. It is found that the optimal solution of the NSLQR problem can be obtained by solving a Pseudo-Differential-Riccati-Equation (PDRE) simultaneously with the closed-loop system equation. A Comparison Theorem for the PDRE is given to facilitate solution methods for the PDRE. A linear time-variant system is employed as an example in simulation to verify the proposed optimal solution. As a non-trivial application, a goal pursuit process in psychology is modeled as a NSLQR problem and two typical goal pursuit behaviors found in human and animals are reproduced using different control weighting . It is found that these two behaviors save control energy and cause less stress over Conventional Control Behavior typified by the LQR control with a constant control weighting , in situations where only the goal discrepancy at the terminal time is of concern, such as in Marathon races and target hitting missions.     

Draft Genome Sequence of a Novel Bacterial Strain,LSJC7, Belonging to the Family Enterobacteriaceae with Dual Resistance to Arsenic and Tetracycline

Strain LSJC7, with dual resistance to arsenic and tetracycline, was isolated from an antimony tailing in China. Its 16S rRNA gene sequence has the highest similarity to that of Enterobacter cloacae subsp. dissolvens LMG 2683^T (97.02%). Here we present the approximately 4.6-Mbp draft genome sequence of strain LSJC7.     

INTRASPECIFIC VARIATION AND THE ROLE OF SUPERPARASITISM IN DIAPAUSE INDUCTION OF TRICHOGRAMMA EVANESCENS WEST-WOOD*

Abstract The diapause of two populations of Trichogramma evanescens Westwood (T. evanescens A and T. evanescens B), collected from different Iranian insect pests, was studied. T. evunescens A in the eggs of Corcyra cephalonica was easily induced to stable diapause with constant 8°C, 15 % and fluctuating temperature (11–23) C -11C. T. evanescens B could not be induced to diapause with the same temperatural regime and host. The experiments showed that the host of maternal generations and the ability of avoiding super-parasitism may play an important role in intraspecific variation of T. evunescens in diapause induction.     

酸敏感离子通道与脑梗死

急性脑梗死约占全部脑卒中的70%,病死率和致残率高,且极易复发。但目前针对急性脑梗死在时间窗内溶栓、抗凝等治疗手段不能从根本上切实有效地修复受损脑组织,且伴有出血等风险。寻找脑梗死形成发展的原因并予以治疗迫在眉睫。酸中毒是引起缺血性脑损伤的重要机制。大量实验研究表明,酸中毒能加重神经元的缺血性损伤,且其梗死面积与酸中毒的程度直接相关。但缺血产生的酸中毒如何引起神经元损伤的确切机制尚不明确。最近研究发现酸中毒能激活一种在中枢及周围神经中广泛存在的膜通道,即酸敏感离子通道,它对Ca2+通透,能引起细胞内Ca2+超载,同时能激活胞内酶引起细胞内蛋白质、脂类及核酸的降解,加重缺血后脑损伤。本文就酸敏感离子通道1a与脑梗死做一综述。