Incorporation of the Tat cell‐penetrating peptide into nanofibers improves the respective antitumor immune response

A major challenge for the development of anticancer vaccines is the induction of a safe and effective immune response, particularly mediated by CD8+ T lymphocytes, in an adjuvant‐free manner. In this respect, we present a simple strategy to improve the specific CD8+ T cell responses using KFE8 nanofibers bearing a Class I (Kb)‐restricted peptide epitope (called E. nanofibers) without the use of adjuvant. We demonstrate that incorporation of Tat, a cell‐penetrating peptide (CPP) of the HIV transactivator protein, into E. nanofibers remarkably enhanced tumor‐specific CD8+ T cell responses. E. nanofibers containing 12.5% Tat peptide (E.Tat_12.5 nanofiber) increased antigen cross‐presentation by bone marrow‐derived dendritic cells as compared with E. nanofibers, or E. nanofibers containing 25 or 50% the Tat peptide. Uptake of KFE8.Tat_12.5 nanofibers by dendritic cells (DCs) was significantly increased compared with KFE8 nanofiber lacking Tat. Peritoneal and lymph node DCs of mice immunized with E.Tat_12.5 nanofibers exhibited increased presentation of the H2kb‐epitope (reminiscent for cross‐presentation) compared with DCs obtained from E. nanofiber vaccinated mice. Tetrameric and intracellular cytokine staining revealed that vaccination with E.Tat_12.5 triggered a robust and specific CD8+ T lymphocyte response, which was more pronounced than in mice vaccinated with E. nanofibers alone. Furthermore, E.Tat_12.5 nanofibers were more potent than E. nanofiber to induce antitumor immune response and tumor‐infiltrating IFN‐γ CD8 T lymphocyte. In terms of cancer vaccine development, we propose that harnessing the nanofiber‐based vaccine platform with incorporated Tat peptide could present a simple and promising strategy to induce highly effective antitumor immune response.     

FGF21 impedes peripheral myelin development by stimulating p38 MAPK/c‐Jun axis

Fibroblast growth factor 21 (FGF21) as a metabolic stress hormone, is mainly secreted by the liver. In addition to its well‐defined roles in energy homeostasis, FGF21 has been shown to promote remyelination after injury in the central nervous system. In the current study, we sought to examine the potential roles of FGF21 in the peripheral nervous system (PNS) myelination. In the PNS myelin development, Fgf21 expression was reversely correlated with myelin gene expression. In cultured primary Schwann cells (SCs), the application of recombinant FGF21 greatly attenuates myelination‐associated gene expression, including Oct6, Krox20, Mbp, Mpz, and Pmp22. Accordingly, the injection of FGF21 into neonatal rats markedly mitigates the myelination in sciatic nerves. On the contrary, the infusion of the anti‐FGF21 antibody accelerates the myelination. Mechanistically, both extracellular signal‐regulated kinase (ERK) and p38 mitogen‐activated protein kinase (MAPK) were stimulated by FGF21 in SCs and sciatic nerves. Following experiments including pharmaceutical intervention and gene manipulation revealed that the p38 MAPK/c‐Jun axis, rather than ERK, is targeted by FGF21 for mediating its repression on myelination in SCs. Taken together, our data provide a new aspect of FGF21 by acting as a negative regulator for the myelin development process in the PNS via activation of p38 MAPK/c‐Jun.     

Site‐specific contribution of Toll‐like receptor 4 to intestinal homeostasis and inflammatory disease

Toll‐like receptor 4 (TLR4) is a highly conserved protein of innate immunity, responsible for the regulation and maintenance of homeostasis, as well as immune recognition of external and internal ligands. TLR4 is expressed on a variety of cell types throughout the gastrointestinal tract, including on epithelial and immune cell populations. In a healthy state, epithelial cell expression of TLR4 greatly assists in homeostasis by shaping the host microbiome, promoting immunoglobulin A production, and regulating follicle‐associated epithelium permeability. In contrast, immune cell expression of TLR4 in healthy states is primarily centred on the maturation of dendritic cells in response to stimuli, as well as adequately priming the adaptive immune system to fight infection and promote immune memory. Hence, in a healthy state, there is a clear distinction in the site‐specific roles of TLR4 expression. Similarly, recent research has indicated the importance of site‐specific TLR4 expression in inflammation and disease, particularly the impact of epithelial‐specific TLR4 on disease progression. However, the majority of evidence still remains ambiguous for cell‐specific observations, with many studies failing to provide the distinction of epithelial versus immune cell expression of TLR4, preventing specific mechanistic insight and greatly impacting the translation of results. The following review provides a critical overview of the current understanding of site‐specific TLR4 activity and its contribution to intestinal/immune homeostasis and inflammatory diseases.     

Long noncoding RNA HNF1A‐AS1 regulates proliferation and apoptosis of glioma through activation of the JNK signaling pathway via miR‐363‐3p/MAP2K4

Long noncoding RNAs (lncRNAs) have been proven to exert important functions in the various biological processes of human cancers. It has been reported that lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A‐AS1) was abnormally expressed and played a role in the initiation and development of various human cancers. In this study, we confirmed that the expression level of HNF1A‐AS1 was increased in glioma tissues and cells. Knockdown of HNF1A‐AS1 inhibited cell proliferation and promoted cell apoptosis in glioma. Then, we disclosed the downregulation of miR‐363‐3p in glioma tissues and cell lines. The interaction between HNF1A‐AS1 and miR‐363‐3p was identified in glioma cells. Furthermore, an inverse correlation between HNF1A‐AS1 and miR‐363‐3p was observed in glioma tissues. Afterwards, we recognized that MAP2K4 was a direct target of miR‐363‐3p. The expression of MAP2K4 was negatively correlated with miR‐363‐3p while positively related to HNF1A‐AS1 in glioma tissues. We also found the regulatory effect of HNF1A‐AS1 on the MAP2K4‐dependent JNK signaling pathway. All findings indicated that HNF1A‐AS1 induces the upregulation of MAP2K4 to activate the JNK signaling pathway to promote glioma cell growth by acting as a miR‐363‐3p sponge.     

Application of machine learning to identify predators of stocked fish in Lake Ontario: using acoustic telemetry predation tags to inform management

Understanding predator–prey interactions and food web dynamics is important for ecosystem-based management in aquatic environments, as they experience increasing rates of human-induced changes, such as the addition and removal of fishes. To quantify the post-stocking survival and predation of a prey fish in Lake Ontario, 48 bloater Coregonus hoyi were tagged with acoustic telemetry predation tags and were tracked on an array of 105 acoustic receivers from November 2018 to June 2019. Putative predators of tagged bloater were identified by comparing movement patterns of six species of salmonids (i.e., predators) in Lake Ontario with the post-predated movements of bloater (i.e., prey) using a random forests algorithm, a type of supervised machine learning. A total of 25 bloater (53% of all detected) were consumed by predators on average (± S.D. ) 3.1 ± 2.1 days after release. Post-predation detections of predators occurred for an average (± S.D. ) of 78.9 ± 76.9 days, providing sufficient detection data to classify movement patterns. Tagged lake trout Salvelinus namaycush provided the most reliable classification from behavioural predictor variables (89% success rate) and was identified as the main consumer of bloater (consumed 50%). Movement networks between predicted and tagged lake trout were significantly correlated over a 6 month period, supporting the classification of lake trout as a common bloater predator. This study demonstrated the ability of supervised learning techniques to provide greater insight into the fate of stocked fishes and predator–prey dynamics, and this technique is widely applicable to inform future stocking and other management efforts.     

Plant–plant facilitation increases with reduced phylogenetic relatedness along an elevation gradient

Environmental conditions can modify the intensity and sign of ecological interactions. The stress gradient hypothesis (SGH) predicts that facilitation becomes more important than competition under stressful conditions. To properly test this hypothesis, it is necessary to account for all (not a subset of) interactions occurring in the communities and consider that species do not interact at random but following a specific pattern. We aim to assess elevational changes in facilitation, in terms of species richness, frequency and intensity of the interaction as a function of the evolutionary relatedness between nurses and their associated species. We sampled nurse and their facilitated plant species in two 1000–2000 m. elevation gradients in Mediterranean Chile where low temperature imposes a mortality filter on seedlings. We first estimated the relative importance of facilitation as a mechanism adding new species to communities distributed along these gradients. We then tested whether the frequency and intensity of facilitation increases with elevation, taking into account the evolutionary relatedness of the nurse species and the facilitated species. We found that nurses increase the species richness of the community by up to 35%. Facilitative interactions are more frequent than competitive interactions (56% versus 44%) and facilitation intensity increased with elevation for interactions involving distantly related lineages. Our results highlight the importance of including an evolutionary dimension in the study of facilitation to have a clearer picture of the mechanisms enabling species to coexist and survive under stressful conditions. This knowledge is especially relevant to conserve vulnerable and threatened communities facing new climate scenarios, such as those located in Mediterranean-type ecosystems.     

葡萄VvIQD10果形相关基因定位及其互作研究

以葡萄6个不同果形品种盛花期花序为材料,通过荧光定量PCR方法分析比较葡萄IQ67结构域(IQ67 domain, IQD)基因家族成员VvIQD10的表达;从椭圆形葡萄品种‘天山’中克隆出VvIQD10基因编码区序列,对其进行生物信息学分析,采用亚细胞定位瞬时表达载体转化烟草的方法研究VvIQD10蛋白在细胞中的分布情况,并通过酵母双杂交实验和双分子荧光互补试验进行蛋白互作研究。结果表明:(1)VvIQD10基因在长果形葡萄品种中的表达量高于近圆形葡萄品种。(2)VvIQD10基因开放阅读框长度为1 401 bp,编码466个氨基酸。(3)VvIQD10蛋白为不稳定亲水性蛋白,无信号肽和跨膜区,但含保守的IQ67结构域,主要结构为α螺旋和随机卷曲,与猕猴桃IQD家族成员(PSS09955.1)亲缘关系最为接近。(4)VvIQD10蛋白主要定位于微管和质膜,并且直接与细胞骨架组织相关蛋白——钙调素类蛋白(VvCML)相互作用。研究认为,VvIQD10基因可能参与葡萄果形调控,葡萄VvCML蛋白从胞质到微管的募集依赖于VvIQD10,推测VvIQD10蛋白可能通过和钙调素类蛋白相结合来调控细胞骨架运动,进而参与葡萄果实形状的变化。     

Autophagy in plants: Physiological roles and post‐translational regulation

In eukaryotes, autophagy helps maintain cellular homeostasis by degrading and recycling cytoplasmic materials via a tightly regulated pathway.Over the past few decades, significant progress has been made towards understanding the physiological functions and molecular regulation of autophagy in plant cells. Increasing evidence indicates that autophagy is essential for plant responses to several developmental and environmental cues, functioning in diverse processes such as senescence, male fertility, root meristem maintenance, responses to nutrient starvation,and biotic and abiotic stress. Recent studies have demonstrated that, similar to nonplant systems,the modulation of core proteins in the plant autophagy machinery by posttranslational modifications such as phosphorylation, ubiquitination,lipidation, S-sulfhydration, S-nitrosylation, and acetylation is widely involved in the initiation and progression of autophagy. Here, we provide an overview of the physiological roles and posttranslational regulation of autophagy in plants.