Positive and negative regulation of the gamma-secretase activity by nicastrin in a murine model

Nicastrin is a component of the gamma-secretase complex that has been shown to adhere to presenilin-1 (PS1), Notch, and APP. Here we demonstrate that Nicastrin-deficient mice showed a phenotype that is indistinguishable from PS1/PS2 double knock-out mice, whereas heterozygotes were healthy and viable. Fibroblasts derived from Nicastrin-deficient embryos were unable to generate amyloid beta-peptide and failed to release the intracellular domain of APP- or Notch1-Gal4-VP16 fusion proteins. Additionally, C- and N-terminal fragments of PS1 and the C-terminal fragments of PS2 were not detectable in Nicastrin-null fibroblasts, whereas full-length PS1 accumulated in null fibroblasts, indicating that Nicastrin is required for the endoproteolytic processing of presenilins. Interestingly, cells derived from Nicastrin heterozygotes produced relatively higher levels of amyloid beta-peptide whether the source was endogenous mouse or transfected human APP. These data demonstrate that Nicastrin is essential for the gamma-secretase cleavage of APP and Notch in mammalian cells and that Nicastrin has both positive and negative functions in the regulation of gamma-secretase activity.     

Quantitative trait loci for morphometric traits in multiple families of common carp (<Emphasis Type="Italic">Cyprinus carpio</Emphasis>)

Quantitative trait locus (QTL) mapping is frequently used to understand the genetic architecture of quantitative traits. Herein, we performed a genome scan for QTL affecting the morphometric characters in eight full-sib families containing 522 individuals using different statistical methods (Sib-pair and half-sib model). A total of 194 QTLs were detected in 25 different regions on 10 linkage groups (LGs). Among them, 37 QTLs on five LGs (eight, 13, 24, 40 and 45) were significant (5% genome-wide level), while the remaining 40 (1% chromosome-wide level) and 117 (5% chromosome-wide level) indicated suggestive effect on those traits. Heritabilities for most morphometric traits were moderate to high, ranging from 0.21 to 0.66, with generally strong phenotypic and genetic correlations between the traits. A large number of QTLs for morphometric traits were co-located, consistent with their high correlations, and may reflect pleiotropic effect on the same genes. Biological pathways were mapped for possible candidate genes on QTL regions. One significantly enriched pathway was identified on LG45, which had a P-value of 0.04 and corresponded to the “regulation of actin cytoskeleton pathway”. The results are expected to be useful in marker-assisted selection (MAS) and provide valuable information for the study of gene pathway for morphometric and growth traits of the common carp.     

Bioactivity-guided isolation of chemical constituents against H2O2-induced neurotoxicity on PC12 from Cimicifuga dahurica (Turcz.) Maxim.

Three new compounds (1, 6, 9), with six known compounds (2–5, 7–8) were obtained from water-soluble extract of Cimicifuga dahurica (Turcz.) Maxim. by bioactivity-guided isolation. Their structures were elucidated by chemical and spectral analysis, including 1D, 2D NMR data and HRESIMS. H₂O₂-induced neurotoxicity on PC12 cells model were conducted to evaluate the neuro-protective capability of these compounds. The piscidic acid derivatives compounds 4–7 showed marked neuro-protective effect at certain concentration.     

Global analysis of canola genes targeted by SHORT HYPOCOTYL UNDER BLUE 1 during endosperm and embryo development

Seed development in dicots includes early endosperm proliferation followed by growth of the embryo to replace the endosperm. Endosperm proliferation in dicots not only provides nutrient supplies for subsequent embryo development but also enforces a space limitation, influencing final seed size. Overexpression of Arabidopsis SHORT HYPOCOTYL UNDER BLUE1::uidA (SHB1:uidA) in canola produces large seeds. We performed global analysis of the canola genes that were expressed and influenced by SHB1 during early endosperm proliferation at 8 days after pollination (DAP) and late embryo development at 13 DAP. Overexpression of SHB1 altered the expression of 973 genes at 8 DAP and 1035 genes at 13 DAP. We also surveyed the global SHB1 association sites, and merging of these sites with the RNA sequencing data identified a set of canola genes targeted by SHB1. The 8‐DAP list includes positive and negative genes that influence endosperm proliferation and are homologous to Arabidopsis MINI3, IKU2, SHB1, AGL62, FIE and AP2. We revealed a major role for SHB1 in canola endosperm development based on the dynamics of SHB1‐altered gene expression, the magnitude of SHB1 chromatin immunoprecipitation enrichment and the over‐representation of eight regulatory genes for endosperm development. Our studies focus on an important agronomic trait in a major crop for global agriculture. The datasets on stage‐specific and SHB1‐induced gene expression and genes targeted by SHB1 also provide a useful resource in the field of endosperm development and seed size engineering. Our practices in an allotetraploid species will impact similar studies in other crop species.     

丛枝菌根真菌促进南美蟛蜞菊生长及对难溶磷的吸收

为了解2种丛枝菌根真菌(AMF)摩西管柄囊霉(Funneliformis mosseae, FM)和地表球囊霉(Glomus versiforme, GV)对入侵植物南美蟛蜞菊(Wedelia trilobata)的生长和对难溶性磷酸盐利用的影响,采用沙培盆栽方式,研究了南美蟛蜞菊在接种AMF与添加难溶性磷酸盐的生长和磷含量的变化。结果表明,在磷限制环境下FM对南美蟛蜞菊的侵染率达55%～69%,GV的侵染率达到63%～80%。添加难溶性磷酸盐后,2种AMF均促进了南美蟛蜞菊茎的伸长(FM:+46%; GV:+65%)、总生物量的增加(FM:+27.2%; GV:+40%)和磷含量的增加(FM:+36.6%; GV:+40.7%)。对比FM,GV对植物利用难溶性磷有更显著的促进作用。因此,南美蟛蜞菊与2种AMF形成的共生体系可以促进植物生长和对营养资源的利用,提高对难溶性磷的吸收效率可能使得南美蟛蜞菊在营养贫乏的环境中更好地建立种群。     

DJ‐1 inhibits autophagy activity of prostate cancer cells by repressing JNK–Bcl2–Beclin1 signaling

The regulation of DJ‐1 on AR signaling plays an important role in the pathogenesis of prostate cancer (PCa). DJ‐1 could alter autophagy and regulate Beclin1‐involved autophagy response through JNK‐dependent pathway. JNK is known to mediate autophagy through Bcl2–Beclin1 complex. Therefore, this study aimed to investigate the significance of autophagy in DJ‐1‐modulated PCa cells. The current studies showed that DJ‐1 overexpression in LNCaP decreased LC3 transformation and autophagosome formation. However, DJ‐1 knockdown exerted the opposite effect. Moreover, DJ‐1 silencing inhibited survival and promoted death in LNCaP, which was recovered by autophagy inhibition with 3‐MA. In addition, DJ‐1 overexpression inhibited the phosphorylation of JNK and Bcl2, and the dissociation of Beclin1 and Bcl2; while the effect of silencing DJ‐1 was completely opposite. More important, JNK activated by anisimycin inhibited the proliferation and promoted death of DJ‐1‐overexpressed LNCaP while increasing LC3 transformation and LC3‐puncta formation, but these results were reversed by the decrease of Beclin1 (by spautin‐1). In contrast, when DJ‐1 was silenced, the death of LNCaP, LC3 transformation, and LC3‐puncta formation were inhibited by JNK inhibitor SP600125, which promoted cell proliferation. However, Bcl2 inhibition (by ABT737) reversed all the effects of SP600125. Our results suggested that DJ‐1 in PCa cells could promote the growth of PCa through autophagy inhibition, and JNK–Bcl2–Beclin1 signaling played an important role in it. The study provided new insights into the role of DJ‐1 in the development of PCa.     

Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss

Changes in mitochondrial dynamics (fusion and fission) are known to occur during stem cell differentiation; however, the role of this phenomenon in tissue aging remains unclear. Here, we report that mitochondrial dynamics are shifted toward fission during aging of Drosophila ovarian germline stem cells (GSCs), and this shift contributes to aging‐related GSC loss. We found that as GSCs age, mitochondrial fragmentation and expression of the mitochondrial fission regulator, Dynamin‐related protein (Drp1), are both increased, while mitochondrial membrane potential is reduced. Moreover, preventing mitochondrial fusion in GSCs results in highly fragmented depolarized mitochondria, decreased BMP stemness signaling, impaired fatty acid metabolism, and GSC loss. Conversely, forcing mitochondrial elongation promotes GSC attachment to the niche. Importantly, maintenance of aging GSCs can be enhanced by suppressing Drp1 expression to prevent mitochondrial fission or treating with rapamycin, which is known to promote autophagy via TOR inhibition. Overall, our results show that mitochondrial dynamics are altered during physiological aging, affecting stem cell homeostasis via coordinated changes in stemness signaling, niche contact, and cellular metabolism. Such effects may also be highly relevant to other stem cell types and aging‐induced tissue degeneration.     

Hollow CuS Nanoboxes as Li‐Free Cathode for High‐Rate and Long‐Life Lithium Metal Batteries

Transition metal sulfides hold promising potentials as Li‐free conversion‐type cathode materials for high energy density lithium metal batteries. However, the practical deployment of these materials is hampered by their poor rate capability and short cycling life. In this work, the authors take the advantage of hollow structure of CuS nanoboxes to accommodate the volume expansion and facilitate the ion diffusion during discharge–charge processes. As a result, the hollow CuS nanoboxes achieve excellent rate performance (≈371 mAh g^?1 at 20 C) and ultra‐long cycle life (>1000 cycles). The structure and valence evolution of the CuS nanobox cathode are identified by scanning electron microscopy, transmission electron microscopy, and X‐ray photoelectron spectroscopy. Furthermore, the lithium storage mechanism is revealed by galvanostatic intermittent titration technique and operando Raman spectroscopy for the initial charge–discharge process and the following reversible processes. These results suggest that the hollow CuS nanobox material is a promising candidate as a low‐cost Li‐free cathode material for high‐rate and long‐life lithium metal batteries.     

Caesalpanins A–C,Three Dimeric Cassane Diterpenoids from the Seeds of Caesalpinia sappan L.

Three dimeric cassane diterpenoids, caesalpanins A–C, were isolated from the seeds of Caesalpinia sappan L., as well as three known compounds. Their structures were determined via analysis of 1D‐, 2D‐NMR, and HR‐ESI‐MS data. Caesalpanins A and B were the second and third compounds that presented a nitrogen‐containing cassane diterpenoid dimer linked through one ether bond between C‐19 and C‐20′. Caesalpanin B exhibited moderate cytotoxic activity against MCF‐7 cell lines with IC₅₀ value of 29.98 μm . Caesalpanins A and B had weak inhibitory effects against LPS‐induced nitric oxide (NO) production in RAW 264.7 macrophages at 50 μm with inhibitory rate of 36.01 % and 32.93 %, respectively.