Two host cytoplasmic effectors are required for pathogenesis of Phytophthora sojae by suppression of host defenses

Phytophthora sojae encodes hundreds of putative host cytoplasmic effectors with conserved FLAK motifs following signal peptides, termed crinkling- and necrosis-inducing proteins (CRN) or Crinkler. Their functions and mechanisms in pathogenesis are mostly unknown. Here, we identify a group of five P. sojae-specific CRN-like genes with high levels of sequence similarity, of which three are putative pseudogenes. Functional analysis shows that the two functional genes encode proteins with predicted nuclear localization signals that induce contrasting responses when expressed in Nicotiana benthamiana and soybean (Glycine max). PsCRN63 induces cell death, while PsCRN115 suppresses cell death elicited by the P. sojae necrosis-inducing protein (PsojNIP) or PsCRN63. Expression of CRN fragments with deleted signal peptides and FLAK motifs demonstrates that the carboxyl-terminal portions of PsCRN63 or PsCRN115 are sufficient for their activities. However, the predicted nuclear localization signal is required for PsCRN63 to induce cell death but not for PsCRN115 to suppress cell death. Furthermore, silencing of the PsCRN63 and PsCRN115 genes in P. sojae stable transformants leads to a reduction of virulence on soybean. Intriguingly, the silenced transformants lose the ability to suppress host cell death and callose deposition on inoculated plants. These results suggest a role for CRN effectors in the suppression of host defense responses.     

An Upgraded Lithium Ion Battery Based on a Polymeric Separator Incorporated with Anode Active Materials

Structural/compositional characteristics at the anode/electrolyte interface are of paramount importance for the practical performance of lithium ion batteries, including cyclic stability, rate capacity, and operational safety. The anode‐electrolyte interface with traditional separator technology is featured with inevitable phase discontinuity and fails to support the stable operation of lithium ion batteries based on large‐capacity anodes with structural change in charges/discharges, such as transition metal oxide anodes. In this work, an anode/electrolyte framework based on an oxide anode and an active‐oxide‐incorporated separator is proposed for the first time and investigated for lithium ion batteries. The architecture builds a robust anode‐separator interface in LIBs, shortens Li⁺ diffusion path, accelerates electron transport, and mitigates the volume change of the oxide anode in electrochemical reactions. Remarkably, 4 wt% CuO addition in the separator leads to a 17% enhancement in the overall capacity of a battery with a CuO anode. The battery delivers an unparalleled record reversible capacity of 637.2 mAh g^?1 with a 99% capacity retention after 100 charge/discharge cycles at 0.5 C. The high performance are attributed to the robust anode‐separator interface, which gives rise to enhanced interaction between the oxide anode and the same‐oxide‐incorporated composite in the separator.     

叶面积指数田间测量中有限长度平均法的改进

叶面积指数(LAI)的田间测量是生态和农业等领域的常规工作之一, 测量方法分为直接测量和间接测量, 间接测量中有一类方法基于数字相机照片提取冠层孔隙率, 再用有限长度平均法同时估算LAI和聚集指数。然而, 有限长度平均法自提出以来缺少进一步的发展, 在有限长度的样线/样方上应用比尔定律的方式具有理论缺陷, 可能造成无效值或高估LAI。从模拟的训练数据中提取经验公式以取代比尔定律进行样线/样方的LAI估算, 提高了有限长度平均法的精度和鲁棒性。进一步分析在一定精度需求下对样线/样方大小和数量的要求, 对于非均匀样地, 提出样线长度为8倍等效叶片边长、样方边长为3倍等效叶片边长的推荐设置。在基于数字相机照片提取非均匀样地LAI的应用中, 使用样方采样比样线采样更为适宜。     

Non-coenzyme role of vitamin B1 in RANKL-induced osteoclastogenesis and ovariectomy induced osteoporosis

Vitamins B are co-enzymes participating in energy metabolic pathways. While some vitamins B are known affecting bone homeostasis, the effects of vitamin B1 (thiamine) on bone health remains unclear. In our study, we used cell counting kit-8, tartrate-resistant acid phosphatase stain, actin cytoskeleton stain, and pit formation assay to evaluate the effect of thiamine on osteoclast differentiation, formation, and function, respectively. Then we used dichloro-dihydro-fluorescein diacetate assay to investigate reactive oxygen species (ROS) generation and removal. Osteoporosis model by ovariectomy was established for animal experiments. We found that thiamine had inhibitory effect on osteoclast differentiation. And its inhibitory role on osteoclast differentiation is in a dose-dependent way. Mechanistically, ThDP suppresses intracellular ROS accumulation and unfolded protein response signaling during osteoclastogenesis via inhibiting Rac-Nox1/2/4 and intracellular inositol-requiring protein-1α/X-box-binding protein pathways, respectively. Osteoporotic mice treated with thiamine rich dietary showed better bone strength relative to thiamine deficient dietary. Our study explored the non-coenzyme inhibitory functions of B1 vitamin in receptor activator of nuclear factor κB ligand induced osteoclastogenesis and uncovered the significance of B1 vitamin in bone health.     

Opposite Role of Tumor Necrosis Factor Receptors in Dextran Sulfate Sodium-Induced Colitis in Mice

Tumor necrosis factor-α (TNF-α) is a key factor for the pathogenesis of inflammatory bowel diseases (IBD), whose function is known to be mediated by TNF receptor 1 (TNFR1) or 2. However, the precise role of the two receptors in IBD remains poorly understood. Herein, acute colitis was induced by dextran sulfate sodium (DSS) instillation in TNFR1 or 2−/− mice. TNFR1 ablation led to exacerbation of signs of colitis, including more weight loss, increased mortality, colon shortening and oedema, severe intestinal damage, and higher levels of myeloperoxidase compared to wild-type counterparts. While, TNFR2 deficiency had opposite effects. This discrepancy was reflected by alteration of proinflammatory cytokine and chemokine production in the colons. Importantly, TNFR1 ablation rendered enhanced apoptosis of colonic epithelial cells and TNFR2 deficiency conferred pro-apoptotic effects of lamina propria (LP)-immune cells, as shown by the decreased ratio of Bcl-2/Bax and enhanced nuclear factor (NF)-κB activity.     

αA Crystallin May Protect against Geographic Atrophy-Meta-Analysis of Cataract vs. Cataract Surgery for Geographic Atrophy and Experimental Studies

Background

Cataract and geographic atrophy (GA, also called advanced “dry” age-related macular degeneration) are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies.

Methods/Principal Findings

We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR) of 3.75 (95% CI: 95% CI: 1.84–7.62). However, cataract surgery is not associated with the risk of geographic atrophy (polled OR = 3.23, 95% CI: 0.63–16.47). Further experiments were performed to analyze how the αA-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that theαA-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO₃ in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in αA-crystallin knockout mice compared to wild-type mice.

Conclusions

Therefore, αA-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA.     

HDAC Inhibitor L-Carnitine and Proteasome Inhibitor Bortezomib Synergistically Exert Anti-Tumor Activity In Vitro and In Vivo

Combinations of proteasome inhibitors and histone deacetylases (HDAC) inhibitors appear to be the most potent to produce synergistic cytotoxicity in preclinical trials. We have recently confirmed that L-carnitine (LC) is an endogenous HDAC inhibitor. In the current study, the anti-tumor effect of LC plus proteasome inhibitor bortezomib (velcade, Vel) was investigated both in cultured hepatoma cancer cells and in Balb/c mice bearing HepG2 tumor. Cell death and cell viability were assayed by flow cytometry and MTS, respectively. Gene, mRNA expression and protein levels were detected by gene microarray, quantitative real-time PCR and Western blot, respectively. The effect of Vel on the acetylation of histone H3 associated with the p21^cip1 gene promoter was examined by using ChIP assay and proteasome peptidase activity was detected by cell-based chymotrypsin-like (CT-like) activity assay. Here we report that (i) the combination of LC and Vel synergistically induces cytotoxicity in vitro; (ii) the combination also synergistically inhibits tumor growth in vivo; (iii) two major pathways are involved in the synergistical effects of the combinational treatment: increased p21^cip1 expression and histone acetylation in vitro and in vivo and enhanced Vel-induced proteasome inhibition by LC. The synergistic effect of LC and Vel in cancer therapy should have great potential in the future clinical trials.     

Evidence of positive selection at codon sites localized in the C-terminal peptide of ORC6

Origin recognition complex 6 (Orc6) plays a central role in the initiation of DNA replication in all eukaryotic systems. The exact contribution of Orc6 to replication initiation has yet to be elucidated. Here, we analyzed the evolutionary dynamics of Orc6 in 15 vertebrates. Positive selection was detected in the region of exon 6 of the Orc6 gene. Site tests revealed a proportion of codon sites that displayed evidence of positive selection (ω > 1) within the coding sequences of the vertebrate Orc6 gene. Seven positively selected amino acid sites were identified and three were located in exon6. These results suggest that amino acid residues present in the middle region of the protein are more selectively constrained, whereas amino acid residues in the C-terminal peptide of the protein evolve at a faster rate, possibly because of heightened selective pressure during the course of evolution.