P38α/β在黑色素瘤细胞辐射应急响应中的作用

P38有丝分裂原激活蛋白激酶(MAPK)在肿瘤的发生发展中的作用仍然存在争议。实验结果显示,P38α/β特异性抑制剂SB202190可以显著增加黑色素瘤细胞的倍增时间、降低细胞的微核率,但对γH2AX foci的形成和克隆存活率并没有明显影响。提示P38α/β可能不影响人黑色素瘤细胞的DNA损伤修复能力及细胞的辐射敏感性,而是通过提高细胞的增殖速率、增加基因组不稳定性来促进人黑色素瘤细胞的恶性发展。     

河南淅川坑南遗址调查发现的石制品

河南淅川坑南遗址位于丹江口库区,丹江口库区是近年来旧石器考古发掘和研究的重点地区。2016年对坑南遗址发掘前,在周边调查发现旧石器时代石制品209件,石制品类型包括石核、石片、石叶和石器等。剥片方法有锤击法和砸击法。石器毛坯类型多为片状,少量为块状、砾石。石器修理方式以正向为主,其次为反向和复向。初步判断其时代最早能到旧石器时代中期。新发现对于探讨晚更新世南北旧石器过渡地带的特点,具有重要意义。     

Targeting UHRF1-SAP30-MXD4 axis for leukemia initiating cell eradication in myeloid leukemia

Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs. Mechanistically, UHRF1 directly interacts with Sin3A-associated protein 30 (SAP30) through two critical amino acids, G572 and F573 in its SRA domain, to repress gene expression. Depletion of UHRF1 or SAP30 derepresses an important target gene, MXD4, which encodes a MYC antagonist, and leads to suppression of leukemogenesis. Further knockdown of MXD4 can rescue the leukemogenesis by activating the MYC pathway. Lastly, we identified a UHRF1 inhibitor, UF146, and demonstrated its significant therapeutic efficacy in the myeloid leukemia PDX model. Taken together, our study reveals the mechanisms for altered epigenetic programs in AML and provides a promising targeted therapeutic strategy against AML.Subject terms: Leukaemia, Cell biology     

细菌的应激反应和生理代谢与耐药性及其控制策略

抗菌药在医疗和畜牧生产中的滥用导致了细菌抗药性的产生,这个公共卫生问题引起了人们越来越多的关注。除了基因突变和获得形成的抗药性(Resistance)外,细菌在自然环境中遇到的各种压力会引发其产生应激反应,这不仅可以保护细菌免受这些压力的影响,还会改变细菌对抗菌药的耐药性(Tolerance)。耐药性的产生必然会影响细菌的生理代谢,但是细菌可以通过调节自身代谢恢复对药物的敏感性。文中综述了近年来细菌应激反应和生理代谢与细菌耐药性之间的相关研究,以期采取更加有效的措施来控制细菌抗药性的发生和蔓延。     

Introduction of broadleaf species into monospecific Cunninghamia lanceolata plantations changed the soil Acidobacteria subgroups composition and nitrogen-cycling gene abundances

Plant and Soil - A model that can assess the structure and functionality of the soil/plant/atmosphere (SPA) continuum along spatial and temporal gradients using specific and measurable variables...