Co‐suppression in Pyropia yezoensis (Rhodophyta) Reveals the Role of PyLHCI in Light Harvesting and Generation Switch

The red macroalga Pyropia yezoensis is an economically important seaweed widely cultured in Asian countries and is a model organism for molecular biological and commercial research. This species is unique in that it utilizes both phycobilisomes and transmembrane light‐harvesting proteins as its antenna system. Here, one of the genes of P. yezoensis (PyLHCI) was selected for introduction into its genome to overexpress PyLHCI. However, the co‐suppression phenomenon occurred. This is the first documentation of co‐suppression in algae, in which it exhibits a different mechanism from that in higher plants. The transformant (T1) was demonstrated to have higher phycobilisomes and lower LHC binding pigments, resulting in a redder color, higher sensitivity to salt stress, smaller in size, and slower growth rate than the wildtype (WT). The photosynthetic performances of T1 and WT showed similar characteristics; however, P700 reduction was slower in T1. Most importantly, T1 could release a high percentage of carpospores in young blades to switch generation during its life cycle, which was rarely seen in WT. The co‐suppression of PyLHCI revealed its key roles in light harvesting, stress resistance, and generation alternation (generation switch from gametophytes to sporophytes, and reproduction from asexual to sexual).     

Linking Physiology To Ecological Function: Environmental Conditions Affect Performance And Size Of The Intertidal Kelp Hedophyllum Sessile (Laminariales,Phaeophyceae)

For autogenic ecosystem engineers, body size is an aspect of individual performance that has direct connections to community structure; yet the complex morphology of these species can make it difficult to draw clear connections between the environment and performance. We combined laboratory experiments and field surveys to test the hypothesis that individual body size was determined by disparate localized physiological responses to environmental conditions across the complex thallus of the intertidal kelp Hedophyllum sessile, a canopy‐forming physical ecosystem engineer. We documented substantial (> 40%) declines in whole‐thallus photosynthetic potential (as Maximum Quantum Yield, MQY) as a consequence of emersion, which were related to greater than 10‐fold increases in intra‐thallus MQY variability (as Coefficient of Variation). In laboratory experiments, desiccation and high light levels during emersion led to lasting impairment of photosynthetic potential and an immediate > 25% reduction in area due to tissue contraction, which was followed by complete loss of structural integrity after three days of submersion. Tissue exposed to desiccation and high light during emersion had higher nitrogen concentrations and lower phlorotannin concentrations than tissue in control treatments (on average 1.36 and 0.1x controls, respectively), suggesting that conditions during emersion have the potential to affect food quality for consumers. Our data indicate that the complex thallus morphology of H. sessile may be critical to this kelp’s ability to persist in the intertidal zone despite the physiological challenges of emersion and encourage a more nuanced view of the concept of “sub‐lethal stress” on the scale of the whole individual.     

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.     

Effects of Radio-Collars are not Contingent on Socioecological Conditions in Degus

Species-specific research on free-ranging mammals reveals a diversity of effects of radio-collars on behavior, body condition, and fitness. Although these studies indicate rather limited direct effects, radio-collars may cause effects influenced by socio-ecological conditions. Using a 7-year study on a natural population of group-living degus (Octodon degus), we tested the hypothesis that ecological (food availability, burrow density) and social (group size, group male-to-female ratio) conditions modulate effects of radio-collars on body condition (e.g., body mass, ecto- and endoparasite loads, fecal cortisol metabolites) and direct fitness (litter size, adult survival). We determined the effect of radio-collar use on degus by contrasting the presence or absence of radio-collars, quantifying the effects of the number of days carrying a radio-collar, and the relative mass of radio-collars worn by degus in central Chile between 2009 and 2015. Radio-collar use was not associated with direct effects on litter size, adult survival, or with body mass and fecal cortisol metabolites but was linked to low ecto- and endoparasite loads. These seemingly positive effects may reflect decreased mobility, or a research bias for radio-collaring larger, healthier individuals. There was no evidence that ecological and social conditions modulated radio-collar effects on degu body condition and direct fitness. These findings are consistent with evidence from other mammal studies that reported no appreciable detrimental direct or indirect effects of radio-collars. © 2021 The Wildlife Society.