Prohibitin is a cholesterol‐sensitive regulator of cell cycle transit

Cholesterol is essential in establishing most functional animal cell membranes; cells cannot grow or proliferate in the absence of sufficient cholesterol. Consequently, almost every cell, tissue, and animal tightly regulates cholesterol homeostasis, including complex mechanisms of synthesis, transport, uptake, and disposition of cholesterol molecules. We hypothesize that cellular recognition of cholesterol insufficiency causes cell cycle arrest in order to avoid a catastrophic failure in membrane synthesis. Here, we demonstrate using unbiased proteomics and standard biochemistry that cholesterol insufficiency causes upregulation of prohibitin, an inhibitor of cell cycle progression, through activation of a cholesterol‐responsive promoter element. We also demonstrate that prohibitin protects cells from apoptosis caused by cholesterol insufficiency. This is the first study tying cholesterol homeostasis to a specific cell cycle regulator that inhibits apoptosis. J. Cell. Biochem. 111: 1367–1374, 2010. © 2010 Wiley‐Liss, Inc.     

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIX^promotor)‐controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIX^promotor‐AIM2 adenoviruses (Ad‐CAIX^promotor‐AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad‐CAIX^promotor, Ad‐CAIX^promotor‐AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786‐O cells or OSRC‐2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC‐2‐xenograft mice. The tumour growth was remarkably inhibited in Ad‐CAIX^promotor‐AIM2‐treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD‐CMK resulted in the reduction of anti‐tumour activity by Ad‐CAIX^promotor‐AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad‐CAIX^promotor‐AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour‐specific Ad‐CAIX^promotor‐AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2‐based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.     

Influence of Polymer Aggregation and Liquid Immiscibility on Morphology Tuning by Varying Composition in PffBT4T‐2DT/Nonfullerene Organic Solar Cells

The temperature‐dependent aggregation behavior of PffBT4T polymers used in organic solar cells plays a critical role in the formation of a favorable morphology in fullerene‐based devices. However, there is little investigation into the impact of donor/acceptor ratio on morphology tuning, especially for nonfullerene acceptors (NFAs). Herein, the influence of composition on morphology is reported for blends of PffBT4T‐2DT with two NFAs, O‐IDTBR and O‐IDFBR. The monotectic phase behavior inferred from differential scanning calorimetry provides qualitative insight into the interplay between solid–liquid and liquid–liquid demixing. Transient absorption spectroscopy suggests that geminate recombination dominates charge decay and that the decay rate is insensitive to composition, corroborated by negligible changes in open‐circuit voltage. Exciton lifetimes are also insensitive to composition, which is attributed to the signal being dominated by acceptor excitons which are formed and decay in domains of similar size and purity irrespective of composition. A hierarchical morphology is observed, where the composition dependence of size scales and scattering intensity from resonant soft X‐ray scattering (R‐SoXS) is dominated by variations in volume fractions of polymer/polymer‐rich domains. Results suggest an optimal morphology where polymer crystallite size and connectivity are balanced, ensuring a high probability of hole extraction via such domains.     

Double the Capacity of Manganese Spinel for Lithium‐Ion Storage by Suppression of Cooperative Jahn–Teller Distortion

The relatively low capacity and capacity fade of spinel LiMn₂O₄ (LMO) limit its application as a cathode material for lithium‐ion batteries. Extending the potential window of LMO below 3 V to access double capacity would be fantastic but hard to be realized, as it will lead to fast capacity loss due to the serious Jahn–Teller distortion. Here using experiments combined with extensive ab initio calculations, it is proved that there is a cooperative effect among individual Jahn–Teller distortions of Mn³⁺O₆ octahedrons in LMO, named as cooperative Jahn–Teller distortion (CJTD) in the text, which is the difficulty to access the capacity beyond one lithium intercalation. It is further proposed that the cationic disordering (excess Li at Mn sites and Li/Mn exchange) can intrinsically suppress the CJTD of Mn³⁺O₆ octahedrons. The cationic disordering can break the symmetry of Mn³⁺ arrangements to disrupt the correlation of distortions arising from individual JT centers and prevent the Mn³⁺? O bonds distorting along one direction. Interestingly, with the suppressed CJTD, the original octahedral vacancies in spinel LMO are activated and can serve as extra Li‐ion storage sites to access the double capacity with good reversible cycling stability in microsized LMO.     

Polymorphism analysis and supertype definition of swine leukocyte antigen class I molecules in three-way crossbred (Landrace,Duroc, and Yorkshire) pigs: implications for the vaccine development of African swine fever virus

正Dear Editor,Swine major histocompatibility complex (MHC) is a highly polymorphic gene in pigs and is also called swine leukocyte antigen (SLA)(Fan et al., 2018). SLA is divided into three major categories, SLA Ⅰ (SLA-1,-2,-3), SLA Ⅱ, and SLA Ⅲ(Smith et al., 2005). SLA Ⅰ plays an important role in cellular immunity which can eliminate viruses and other foreign     

Setosphaeria turcica ATR turns off appressorium-mediated maize infection and triggers melanin-involved self-protection in response to genotoxic stress

Eukaryotic organisms activate conserved signalling networks to maintain genomic stability in response to DNA genotoxic stresses. However, the coordination of this response pathway in fungal pathogens remains largely unknown. In the present study, we investigated the mechanism by which the northern corn leaf blight pathogen Setosphaeria turcica controls maize infection and activates self-protection pathways in response to DNA genotoxic insults. Appressorium-mediated maize infection by S. turcica was blocked by the S-phase checkpoint. This repression was dependent on the checkpoint central kinase Ataxia Telangiectasia and Rad3 related (ATR), as inhibition of ATR activity or knockdown of the ATR gene recovered appressorium formation in the presence of genotoxic reagents. ATR promoted melanin biosynthesis in S. turcica as a defence response to stress. The melanin biosynthesis genes StPKS and StLac2 were induced by the ATR-mediated S-phase checkpoint. The responses to DNA genotoxic stress were conserved in a wide range of phytopathogenic fungi, including Cochliobolus heterostrophus, Cochliobolus carbonum, Alternaria solani, and Alternaria kikuchiana, which are known causal agents for plant diseases. We propose that in response to genotoxic stress, phytopathogenic fungi including S. turcica activate an ATR-dependent pathway to suppress appressorium-mediated infection and induce melanin-related self-protection in addition to conserved responses in eukaryotes.     

A high‐throughput BAC end analysis protocol (BAC‐anchor) for profiling genome assembly and physical mapping

Traditional approaches for sequencing insertion ends of bacterial artificial chromosome (BAC) libraries are laborious and expensive, which are currently some of the bottlenecks limiting a better understanding of the genomic features of auto‐ or allopolyploid species. Here, we developed a highly efficient and low‐cost BAC end analysis protocol, named BAC‐anchor, to identify paired‐end reads containing large internal gaps. Our approach mainly focused on the identification of high‐throughput sequencing reads carrying restriction enzyme cutting sites and searching for large internal gaps based on the mapping locations of both ends of the reads. We sequenced and analysed eight libraries containing over 3 200 000 BAC end clones derived from the BAC library of the tetraploid potato cultivar C88 digested with two restriction enzymes, Cla I and Mlu I. About 25% of the BAC end reads carrying cutting sites generated a 60–100 kb internal gap in the potato DM reference genome, which was consistent with the mapping results of Sanger sequencing of the BAC end clones and indicated large differences between autotetraploid and haploid genotypes in potato. A total of 5341 Cla I‐ and 165 Mlu I‐derived unique reads were distributed on different chromosomes of the DM reference genome and could be used to establish a physical map of target regions and assemble the C88 genome. The reads that matched different chromosomes are especially significant for the further assembly of complex polyploid genomes. Our study provides an example of analysing high‐coverage BAC end libraries with low sequencing cost and is a resource for further genome sequencing studies.