FUNDC1 regulates mitochondrial dynamics at the ER–mitochondrial contact site under hypoxic conditions

In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER–mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to recruit autophagosomes, but the mechanisms integrating these processes are poorly understood. Here, we describe a new pathway mediating mitochondrial fission and subsequent mitophagy under hypoxic conditions. FUNDC1 accumulates at the MAM by associating with the ER membrane protein calnexin. As mitophagy proceeds, FUNDC1/calnexin association attenuates and the exposed cytosolic loop of FUNDC1 interacts with DRP1 instead. DRP1 is thereby recruited to the MAM, and mitochondrial fission then occurs. Knockdown of FUNDC1, DRP1, or calnexin prevents fission and mitophagy under hypoxic conditions. Thus, FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells.     

Unattached kinetochores rather than intrakinetochore tension arrest mitosis in taxol-treated cells

Kinetochores attach chromosomes to the spindle microtubules and signal the spindle assembly checkpoint to delay mitotic exit until all chromosomes are attached. Light microscopy approaches aimed to indirectly determine distances between various proteins within the kinetochore (termed Delta) suggest that kinetochores become stretched by spindle forces and compact elastically when the force is suppressed. Low Delta is believed to arrest mitotic progression in taxol-treated cells. However, the structural basis of Delta remains unknown. By integrating same-kinetochore light microscopy and electron microscopy, we demonstrate that the value of Delta is affected by the variability in the shape and size of outer kinetochore domains. The outer kinetochore compacts when spindle forces are maximal during metaphase. When the forces are weakened by taxol treatment, the outer kinetochore expands radially and some kinetochores completely lose microtubule attachment, a condition known to arrest mitotic progression. These observations offer an alternative interpretation of intrakinetochore tension and question whether Delta plays a direct role in the control of mitotic progression.     

A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle and mesenchymal stem cell defects

The segmental premature aging disease Hutchinson-Gilford Progeria syndrome (HGPS) is caused by a truncated and farnesylated form of Lamin A called progerin. HGPS affects mesenchymal lineages, including the skeletal system, dermis, and vascular smooth muscle (VSMC). To understand the underlying molecular pathology of HGPS, we derived induced pluripotent stem cells (iPSCs) from HGPS dermal fibroblasts. The iPSCs were differentiated into neural progenitors, endothelial cells, fibroblasts, VSMCs, and mesenchymal stem cells (MSCs). Progerin levels were highest in MSCs, VSMCs, and fibroblasts, in that order, with these lineages displaying increased DNA damage, nuclear abnormalities, and HGPS-VSMC accumulating numerous calponin-staining inclusion bodies. Both HGPS-MSC and -VSMC viability was compromised by stress and hypoxia in vitro and in vivo (MSC). Because MSCs reside in low oxygen niches in vivo, we propose that, in HGPS, this causes additional depletion of the MSC pool responsible for replacing differentiated cells lost to progerin toxicity.     

Lithium Doping to Enhance Thermoelectric Performance of MgAgSb with Weak Electron–Phonon Coupling

Despite the unfavorable band structure with twofold degeneracy at the valence band maximum, MgAgSb is still an excellent p‐type thermoelectric material for applications near room temperature. The intrinsically weak electron–phonon coupling, reflected by the low deformation potential E_def ≈ 6.3 eV, plays a crucial role in the relatively high power factor of MgAgSb. More importantly, Li is successfully doped into Mg site to tune the carrier concentration, leading to the resistivity reduction by a factor of 3 and a consequent increase in power factor by ≈30% at 300 K. Low lattice thermal conductivity can be simultaneously achieved by all‐scale hierarchical phonon scattering architecture including high density of dislocations and nanoscale stacking faults, nanoinclusions, and multiscale grain boundaries. Collectively, much higher average power factor ≈25 μW cm^?1 K^?2 with a high average ZT ≈ 1.1 from 300 to 548 K is achieved for 0.01 Li doping, which would result in a high output power density ≈1.56 W cm^?2 and leg efficiency ≈9.2% by calculations assuming cold‐side temperature T_c = 323 K, hot‐side temperature T_h = 548 K, and leg length = 2 mm.     

Mass transport in a microchannel bioreactor with a porous wall

A two-dimensional flow model has been developed to simulate mass transport in a microchannel bioreactor with a porous wall. A two-domain approach, based on the finite volume method, was implemented. For the fluid part, the governing equation used was the Navier-Stokes equation; for the porous medium region, the generalized Darcy-Brinkman-Forchheimer extended model was used. For the porous-fluid interface, a stress jump condition was enforced with a continuity of normal stress, and the mass interfacial conditions were continuities of mass and mass flux. Two parameters were defined to characterize the mass transports in the fluid and porous regions. The porous Damkohler number is the ratio of consumption to diffusion of the substrates in the porous medium. The fluid Damkohler number is the ratio of the substrate consumption in the porous medium to the substrate convection in the fluid region. The concentration results were found to be well correlated by the use of a reaction-convection distance parameter, which incorporated the effects of axial distance, substrate consumption, and convection. The reactor efficiency reduced with reaction-convection distance parameter because of reduced reaction (or flux), and smaller local effectiveness factor due to the lower concentration in Michaelis-Menten type reactions. The reactor was more effective, and hence, more efficient with the smaller porous Damkohler number. The generalized results could find applications for the design of bioreactors with a porous wall.     

铝胁迫对入侵植物北美车前生长特性和生物量分配的影响

探讨了铝胁迫对入侵植物北美车前生长特性和生物量分配的影响.结果表明:低浓度( 100 mg/L)的铝胁迫处理对北美车前的生长无显著影响,高浓度(2 000 mg/L)使植株叶片数减少、叶面积变小;短时间高浓度铝胁迫促进北美车前的抽穗数,长时间(30 d)铝胁迫处理后穗生长受到抑制,这种抑制作用在高浓度铝胁迫处理下表现尤...     

Retracted: Downregulated microRNA-224 aggravates vulnerable atherosclerotic plaques and vascular remodeling in acute coronary syndrome through activation of the TGF-β/Smad pathway

Recent studies have shown that circulating microRNAs (miRNA) play a critical role in diagnosing acute coronary syndrome (ACS). This study aims to investigate the effect of miR-224 on atherosclerotic plaques forming and vascular remodeling in ACS and its relationship with TGF-β/Smad pathway. Myocardial infarction (MI) rat model was established and lentivirus vector of miR-224 inhibitor was prepared for investigating the effect of downregulated miR-224 on the contents of nitric oxide (NO) and endothelin-1 (ET-1), blood lipid levels and inflammatory factor levels in serum as well as the TGF-β/Smad pathway. The rats suffering from MI had decreased survival rates and exhibited reduced levels of NO, high-density lipoprotein cholesterol, and lumen diameter, and Smad7 messenger RNA (mRNA) and protein expression; while had significantly increased ratio of heart weight or body weight, levels of ET-1, inflammatory factors, blood lipid indexes, vascular remodeling indexes, collagen volume fraction, vulnerable atherosclerotic plaque area, VCAM-1 and MMP-2 protein expression, TGF-β, Smad2, Smad3, and Smad4 mRNA and protein expression. After inhibiting the TGF-β/Smad pathway, the rats suffering from MI showed notably opposite trend. In conclusion, downregulation of miR-224 expression promotes the formation of vulnerable atherosclerotic plaques and vascular remodeling in ACS through activation of the TGF-β/Smad pathway. Therefore, this study provides a new therapeutic target for ACS.     

拟南芥过氧化物酶序列与功能的生物信息学分析

植物过氧化物酶(POD)属于多基因家族,不仅是植物体内清除活性氧自由基的重要酶类之一,而且参与多种生理生化过程,在维系植物生长发育过程中发挥重要的作用。采用生物信息学方法对拟南芥过氧化物酶家族的73个基因编码的蛋白质序列的结构和功能进行了分析,其中包含氨基酸的数量、等电点、跨膜结构域、信号肽、二级结构组成及磷酸化位点等,并用Mega4.0软件构建了去除信号肽前后的系统进化树,旨在了解其结构特征。对已经进行功能研究的成员进行结构分析,以此来揭示结构与功能之间的联系,为植物抵御氧化胁迫方面研究提供理论基础。     

Enhanced resistance to sclerotinia stem rot in transgenic soybean that overexpresses a wheat oxalate oxidase

Sclerotinia stem rot (SSR), caused by the oxalate-secreting necrotrophic fungal pathogen Sclerotinia sclerotiorum, is one of the devastating diseases that causes significant yield loss in soybean (Glycine max). Until now, effective control of the pathogen is greatly limited by a lack of strong resistance in available commercial soybean cultivars. In this study, transgenic soybean plants overexpressing an oxalic acid (OA)-degrading oxalate oxidase gene OXO from wheat were generated and evaluated for their resistance to S. sclerotiorum. Integration and expression of the transgene were confirmed by Southern and western blot analyses. As compared with non-transformed (NT) control plants, the transgenic lines with increased oxalate oxidase activity displayed significantly reduced lesion sizes, i.e., by 58.71–82.73% reduction of lesion length in a detached stem assay (T₃ and T₄ generations) and 76.67–82.0% reduction of lesion area in a detached leaf assay (T₄ generation). The transgenic plants also showed increased tolerance to the externally applied OA (60 mM) relative to the NT controls. Consecutive resistance evaluation further confirmed an enhanced and stable resistance to S. sclerotiorum in the T₃ and T₄ transgenic lines. Similarly, decreased OA content and increased hydrogen peroxide (H₂O₂) levels were also observed in the transgenic leaves after S. sclerotiorum inoculation. Quantitative real-time polymerase chain reaction analysis revealed that the expression level of OXO reached a peak at 1 h and 4 h after inoculation with S. sclerotiorum. In parallel, a significant up-regulation of the hypersensitive response-related genes GmNPR1-1, GmNPR1-2, GmSGT1, and GmRAR occurred, eventually induced by increased release of H₂O₂ at the infection sites. Interestingly, other defense-related genes such as salicylic acid-dependent genes (GmPR1, GmPR2, GmPR3, GmPR5, GmPR12 and GmPAL), and ethylene/jasmonic acid-dependent genes (GmAOS, GmPPO) also exhibited higher expression levels in the transgenic plants than in the NT controls. Our results demonstrated that overexpression of OXO enhances SSR resistance by degrading OA secreted by S. sclerotiorum and increasing H₂O₂ levels, and eliciting defense responses mediated by multiple signaling pathways.