Brain-Derived Neurotrophic Factor Increases Synaptic Protein Levels via the MAPK/Erk Signaling Pathway and Nrf2/Trx Axis Following the Transplantation of Neural Stem Cells in a Rat Model of Traumatic Brain Injury

Brain-derived neurotrophic factor (BDNF) plays an important role in promoting the growth, differentiation, survival and synaptic stability of neurons. Presently, the transplantation of neural stem cells (NSCs) is known to induce neural repair to some extent after injury or disease. In this study, to investigate whether NSCs genetically modified to encode the BDNF gene (BDNF/NSCs) would further enhance synaptogenesis, BDNF/NSCs or naive NSCs were directly engrafted into lesions in a rat model of traumatic brain injury (TBI). Immunohistochemistry, western blotting and RT-PCR were performed to detect synaptic proteins, BDNF-TrkB and its downstream signaling pathways, at 1, 2, 3 or 4 weeks after transplantation. Our results showed that BDNF significantly increased the expression levels of the TrkB receptor gene and the phosphorylation of the TrkB protein in the lesions. The expression levels of Ras, phosphorylated Erk1/2 and postsynaptic density protein-95 were elevated in the BDNF/NSCs-transplanted groups compared with those in the NSCs-transplanted groups throughout the experimental period. Moreover, the nuclear factor (erythroid-derived 2)-like 2/Thioredoxin (Nrf2/Trx) axis, which is a specific therapeutic target for the treatment of injury or cell death, was upregulated by BDNF overexpression. Therefore, we determined that the increased synaptic proteins level implicated in synaptogenesis might be associated with the activation of the MAPK/Erk1/2 signaling pathway and the upregulation of the antioxidant agent Trx modified by BDNF-TrkB following the BDNF/NSCs transplantation after TBI.     

A comprehensive gene network for fine tuning floral development in poplar

Herbaceous model species, especially Arabidopsis has provided a wealth of information about the genes involved in floral induction and development of inflorescences and flowers. While the genus Populus is an important model system for the molecular biology of woody plant. These two genuses differ in many ways. This study was designed to improve understanding of flower development in poplar at a system level, as its regulatory pathway to a large extent remains poorly known, owing to the presently limited mutant pool. To address this issue, a poplar GeneChip was employed to detect genes expressed during the whole floral developmental process. Using the expressed floral genes, a systematic gene network was constructed with the aid of functional association with Arabidopsis. The results suggested that autonomous, gibberellin, vernalization, photoperiod, ethylene, brassinosteroid, stress-induced and floral suppression pathways are involved in poplar flowering. Modularity analysis revealed several pathways in common with Arabidopsis, such as autonomous, gibberellin, vernalization and photoperiod pathways. In addition, brassinosteroid, stress-induced and floral suppression pathways were implicated as additional novel pathways. Notably, a difference in vernalization between Arabidopsis and poplar was revealed. Autonomous, gibberellin, vernalization, photoperiod, ethylene, brassinosteroid, stress-induced and floral suppression pathways integrated into a systematic gene network in floral development of poplar. Compared to Arabidopsis, brassinosteroid, stress-induced and floral suppression pathways are additional in poplar, and FLC is absent in vernalization pathway in poplar. Preliminary conclusions drawn here provide a basis for both identification of key genes and elucidation of molecular mechanisms involved in poplar floral development.     

Di‐Spiro‐Based Hole‐Transporting Materials for Highly Efficient Perovskite Solar Cells

Hole‐transporting materials (HTMs) are essential for enabling highly efficient perovskite solar cells (PVSCs) to extract and transport the hole carriers. Among numerous HTMs that are studied so far, the single‐spiro‐based compounds are the most frequently used HTMs for achieving highly efficient PVSCs. In fact, all the new spiro‐based HTMs reported so far that render PVSCs over 20% are based on spiro[fluorene‐9,9′‐xanthene] or spiro [cyclopenta [2,1‐b:3,4b′]dithiophene‐4,9′‐fluorene] cores; therefore, there is a need to diversify the design of their structures for further improving their function and performance. In addition, the fundamental understanding of structure–performance relationships for the spiro‐based HTMs is still lagging, for example, how molecular configuration, spiro numbers, and heteroatoms in spiro‐rings impact the efficacy of HTMs. To address these needs, two novel H‐shaped HTMs, G1 and G2 based on the di‐spiro‐rings as the cores are designed and synthesized. The combined good film‐forming properties, better interactions with perovskite, slightly deeper highest occupied molecular orbital, higher mobility and conductivity, as well as more efficient charge transfer for G2 help devices reach a very impressive power conversion efficiency of 20.2% and good stability. This is the first report of demonstrating the feasibility of using di‐spiro‐based HTMs for highly efficient PVSCs.     

Epirubicin induces apoptosis in osteoblasts through death-receptor and mitochondrial pathways

Epirubicin is an anthracycline and is widely used in tumor treatment, but has toxic and undesirable side effects on wide range of cells and hematopoietic stem cells (HSC). Osteoblasts play important roles in bone development and in supporting HSC differentiation and maturation. It remains unknown whether epirubicin-induced bone loss and hematological toxicity are associated with its effect on osteoblasts. In primary osteoblast cell cultures, epirubicin inhibited cell growth and decreased mineralization. Moreover, epirubicin arrested osteoblasts in the G2/M phase, and this arrest was followed by apoptosis in which both the extrinsic (death receptor-mediated) and intrinsic (mitochondrial-mediated) apoptotic pathways were evoked. The factors involved in the extrinsic apoptotic pathway were increased FasL and FADD as well as activated caspase-8. Those involved in the intrinsic apoptotic pathway were decreased Bcl-2; increased reactive oxygen species, Bax, cytochrome c; and activated caspase-9 and caspase-3. These results demonstrate that epirubicin induced osteoblast apoptosis through the extrinsic and intrinsic apoptotic pathways, leading to the destruction of osteoblasts and consequent lessening of their functions in maintaining bone density and supporting hematopoietic stem cell differentiation and maturation.     

Iron metabolism in diabetes-induced Alzheimer’s disease: a focus on insulin resistance in the brain

Alzheimer’s disease (AD) is characterized by an excessive accumulation of toxic amyloid beta (Aβ) plaques and memory dysfunction. The onset of AD is influenced by age, genetic background, and impaired glucose metabolism in the brain. Several studies have demonstrated that diabetes involving insulin resistance and glucose tolerance could lead to AD, ultimately resulting in cognitive dysfunction. Even though the relationship between diabetes and AD was indicated by significant evidences, the critical mechanisms and metabolic alterations in diabetes induced AD are not clear until now. Recently, iron metabolism has been shown to play multiple roles in the central nervous system (CNS). Iron deficiency and overload are associated with neurodegenerative diseases. Iron binds to Aβ and subsequently regulates Aβ toxicity in the CNS. In addition, previous studies have shown that iron is involved in the aggravation of insulin resistance. Considering these effects of iron metabolism in CNS, we expect that iron metabolism may play crucial roles in diabetic AD brain. Thus, we review the recent evidence regarding the relationship between diabetes-induced AD and iron metabolism.     

来源于泗阳鞘氨醇杆菌的聚磷酸激酶的克隆表达及在ATP再生系统中的应用

聚磷酸激酶(polyphosphate kinase,PPK)在体外催化合成ATP的反应中有着重要作用。为寻找能利用短链聚磷酸盐(polyphosphate,polyP)为底物高效合成ATP的聚磷酸激酶,本文以来源于泗阳鞘氨醇杆菌(Sphingobacterium siyangensis)的聚磷酸激酶(PPK2)为研究目标,利用pET-29a构建重组质粒,在大肠杆菌(Escherichia coli)BL21(DE3)中表达,并将其作为ATP再生系统的关键酶与l-氨基酸连接酶(YwfE)联用生产丙谷二肽(Ala-Gln)。ppk2长度为810bp,编码270个氨基酸;SDS-PAGE结果表明PPK2为可溶性表达,分子量为29.7kDa。对PPK2的最适反应条件进行了优化,结果发现其在22–42℃、pH7–10的范围内均可以保持较好活性,且在37℃、pH为7、镁离子(Mg²⁺)浓度为30mmol/L、底物ADP与六偏磷酸钠浓度分别为5mmol/L和10mmol/L时酶活最大,在0.5h时ATP产率可以达到理论值的60%以上。作为模式反应体系,当PPK2与YwfE联用生产Ala-Gln时,达到与直接添加ATP相同的效果。此聚磷酸激酶作为ATP再生系统具有较好的适用性,适用的温度和pH范围广,且能以廉价易得的短链polyP为底物高效合成ATP,为依赖ATP的催化反应体系的能量再生提供了新酶的来源。     

Negative relationships between species richness and evenness render common diversity indices inadequate for assessing long-term trends in butterfly diversity

Species richness and evenness, the two principle components of species diversity, are frequently used to describe variation in species assemblages in space and time. Compound indices, including variations of both the Shannon–Wiener index and Simpson’s index, are assumed to intelligibly integrate species richness and evenness into all-encompassing measures. However, the efficacy of compound indices is disputed by the possibility of inverse relationships between species richness and evenness. Past studies have assessed relationships between various diversity measures across survey locations for a variety of taxa, often finding species richness and evenness to be inversely related. Butterflies are one of the most intensively monitored taxa worldwide, but have been largely neglected in such studies. Long-term butterfly monitoring programs provide a unique opportunity for analyzing how trends in species diversity relate to habitat and environmental conditions. However, analyzing trends in butterfly diversity first requires an assessment of the applicability of common diversity measures to butterfly assemblages. To accomplish this, we quantified relationships between butterfly diversity measures estimated from 10 years of butterfly population data collected in the North Saskatchewan River Valley in Edmonton, Alberta, Canada. Species richness and evenness were inversely related within the butterfly assemblage. We conclude that species evenness may be used in conjunction with richness to deepen our understandings of assemblage organization, but combining these two components within compound indices does not produce measures that consistently align with our intuitive sense of species diversity.     

Chondroitin sulfates and their binding molecules in the central nervous system

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases.     

Lipid droplet proteins and metabolic diseases

Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which are composed of a neutral lipid core bounded by a protein decorated phospholipid monolayer. Although lipid storage is their most obvious function, LDs are far from inert as they participate in maintaining lipid homeostasis through lipid synthesis, metabolism, and transportation. Furthermore, they are involved in cell signaling and other molecular events closely associated with human disease such as dyslipidemia, obesity, lipodystrophy, diabetes, fatty liver, atherosclerosis, and others. The last decade has seen a great increase in the attention paid to LD biology. Regardless, many fundamental features of LD biology remain obscure. In this review, we will discuss key aspects of LD biology including their biogenesis, growth and regression. We will also summarize the current knowledge about the role LDs play in human disease, especially from the perspective of the dynamics of the associated proteins. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.