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Endoplasmic reticulum (ER) homeostasis plays a vital role in cell physiological functions. Various factors can destroy the homeostasis of the ER and cause ER stress. Moreover, ER stress is often related to inflammation. Glucose-regulated protein 78 (GRP78) is an ER chaperone, which plays a vital role in maintaining cellular homeostasis. Nevertheless, the potential effects of GRP78 on ER stress and inflammation is still not fully elucidated in fish. In the present study, ER stress and inflammation was induced by tunicamycin (TM) or palmitic acid (PA) in the macrophages of large yellow croakers. GRP78 was treated with an agonist/inhibitor before or after the TM/PA treatment. The results showed that the TM/PA treatment could significantly induce ER stress and an inflammatory response in the macrophages of large yellow croakers whereas the incubation of the GRP78 agonist could reduce TM/PA-induced ER stress and an inflammatory response. Moreover, the incubation of the GRP78 inhibitor could further induce TM/PA-induced ER stress and an inflammatory response. These results provide an innovative idea to explain the relationship between GRP78 and TM/PA-induced ER stress or inflammation in large yellow croakers. [ABSTRACT FROM AUTHOR]

Peanut is one of the most important oil crops in the world, the growth and productivity of which are severely affected by salt stress. 24-epibrassinolide (EBL) plays an important role in stress resistances. However, the roles of exogenous EBL on the salt tolerance of peanut remain unclear. In this study, peanut seedlings treated with 150 mM NaCl and with or without EBL spray were performed to investigate the roles of EBL on salt resistance. Under 150 mM NaCl conditions, foliar application of 0.1 µM EBL increased the activity of catalase and thereby could eliminate reactive oxygen species (ROS). Similarly, EBL application promoted the accumulation of proline and soluble sugar, thus maintaining osmotic balance. Furthermore, foliar EBL spray enhanced the total chlorophyll content and high photosynthesis capacity. Transcriptome analysis showed that under NaCl stress, EBL treatment up-regulated expression levels of genes encoding peroxisomal nicotinamide adenine dinucleotide carrier (PMP34), probable sucrose-phosphate synthase 2 (SPS2) beta-fructofuranosidase (BFRUCT1) and Na+/H+ antiporters (NHX7 and NHX8), while down-regulated proline dehydrogenase 2 (PRODH). These findings provide valuable resources for salt resistance study in peanut and lay the foundation for using BR to enhance salt tolerance during peanut production. [ABSTRACT FROM AUTHOR]

HIV-1 vaccines have been challenging to develop, partly due to the high level of genetic variation in its genome. Thus, a vaccine that can induce cross-reactive neutralization activities will be needed. Studies on the co-evolution of antibodies and viruses indicate that mimicking the natural infection is likely to induce broadly neutralizing antibodies (bnAbs). We generated the consensus Env sequence for each time point in subject CH505, who developed broad neutralization activities, and selected five critical time points before broad neutralization was detected. These consensus sequences were designed to express stable Env trimers. Priming with the transmitted/founder Env timer and sequential boosting with these consensus Env trimers from different time points induced broader and more potent neutralizing activities than the BG505 Env trimer in guinea pigs. Analysis of the neutralization profiles showed that sequential immunization of Env trimers favored nAbs with gp120/gp41 interface specificity while the BG505 Env trimer favored nAbs with V2 specificity. The unique features such as consensus sequences, stable Env trimers and the sequential immunization to mimic natural infection likely has allowed the induction of improved neutralization responses. [ABSTRACT FROM AUTHOR]

Verticillum dahliae is a soil-borne phytopathogenic fungus causing destructive Verticillium wilt disease. We previously found a trehalase-encoding gene (VdPT1) in V. dahliae being significantly up-regulated after sensing root exudates from a susceptible cotton variety. In this study, we characterized the function of VdPT1 in the growth and virulence of V. dahliae using its deletion-mutant strains. The VdPT1 deletion mutants (ΔVdPT1) displayed slow colony expansion and mycelial growth, reduced conidial production and germination rate, and decreased mycelial penetration ability and virulence on cotton, but exhibited enhanced stress resistance, suggesting that VdPT1 is involved in the growth, pathogenesis, and stress resistance of V. dahliae. Host-induced silencing of VdPT1 in cotton reduced fungal biomass and enhanced cotton resistance against V. dahliae. Comparative transcriptome analysis between wild-type and mutant identified 1480 up-regulated and 1650 down-regulated genes in the ΔVdPT1 strain. Several down-regulated genes encode plant cell wall-degrading enzymes required for full virulence of V. dahliae to cotton, and down-regulated genes related to carbon metabolism, DNA replication, and amino acid biosynthesis seemed to be responsible for the decreased growth of the ΔVdPT1 strain. In contrast, up-regulation of several genes related to glycerophospholipid metabolism in the ΔVdPT1 strain enhanced the stress resistance of the mutated strain. [ABSTRACT FROM AUTHOR]

Natriuretic peptides (NPs) induce vasodilation, natriuresis, and diuresis, counteract the renin–angiotensin–aldosterone system and autonomic nervous system, and are key regulators of cardiovascular volume and pressure homeostasis. Baroreflex afferent pathway is an important reflex loop in the neuroregulation of blood pressure (BP), including nodose ganglion (NG) and nucleus tractus solitarius (NTS). Dysfunction of baroreflex would lead to various hypertensions. Here, we carried out functional experiments to explore the effects of NPs on baroreflex afferent function. Under physiological and hypertensive condition (high-fructose drinking-induced hypertension, HFD), BP was reduced by NPs through NG microinjection and baroreflex sensitivity (BRS) was enhanced via acute intravenous NPs injection. These anti-hypertensive effects were more obvious in female rats with the higher expression of NPs and its receptor A/B (NPRA/NPRB) and lower expression of its receptor C (NPRC). However, these effects were not as obvious as those in HFD rats compared with the same gender control group, which is likely to be explained by the abnormal expression of NPs and NPRs in the hypertensive condition. Our data provide additional evidence showing that NPs play a crucial role in neurocontrol of BP regulation via baroreflex afferent function and may be potential targets for clinical management of metabolic-related hypertension. [ABSTRACT FROM AUTHOR]

Upland cotton (Gossypium hirsutum L.) is one of the important fiber crops. Cotton flowers usually appear white (or cream-colored) without colored spots at the petal base, and turn pink on the next day after flowering. In this study, using a mutant showing pink petals with crimson spots at their base, we conducted comparative metabolome and transcriptome analyses to investigate the molecular mechanism of coloration in cotton flowers. Metabolic profiling showed that cyanidin-3-O-glucoside and glycosidic derivatives of pelargonidins and peonidins are the main pigments responsible for the coloration of the pink petals of the mutant. A total of 2443 genes differentially expressed (DEGs) between the white and pink petals were identified by RNA-sequencing. Many DEGs are structural genes and regulatory genes of the anthocyanin biosynthesis pathway. Among them, MYB21, UGT88F3, GSTF12, and VPS32.3 showed significant association with the accumulation of cyanidin-3-O-glucoside in the pink petals. Taken together, our study preliminarily revealed the metabolites responsible for the pink petals and the key genes regulating the biosynthesis and accumulation of anthocyanins in the pink petals. The results provide new insights into the biochemical and molecular mechanism underlying anthocyanin biosynthesis in upland cotton. [ABSTRACT FROM AUTHOR]

Mepiquat chloride (MC) is a plant growth regulator widely used in cotton production to control vegetative overgrowth of cotton plants to achieve ideal plant architecture required for high yielding. Cotton varieties respond differently to MC application, but there is little information about the molecular mechanisms underlying the varietal difference. In this study, comparative transcriptome analysis was conducted by using two Upland cotton varieties with different sensitivity (XLZ74, insensitive; SD1068, sensitive) to MC treatment, aiming to understand the molecular mechanisms responsible for varietal difference of MC sensitivity. RNA-seq data were generated from the two varieties treated with MC or water at three time points, 1, 3 and 6 days post-spray (dps). Genes differentially expressed between the MC and mock treatments of XLZ74 (6252) and SD1068 (6163) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to compare the enriched GO terms and KEGG pathways between the two varieties. Signal transduction of phytohormones, biosynthesis of gibberellins (GAs) and brassinosteroids (BRs) and profiles of transcription factors (TFs) seemed to be differentially affected by MC in the two varieties. The transcriptomic results were further consolidated with the content changes of phytohormones in young stem. Several GA catabolic genes, GA2ox, were highly induced by MC in both varieties especially in SD1068, consistent with a more significant decrease in GA4 in SD1068. Several AUX/IAA and SAUR genes and CKX genes were induced by MC in both varieties, but with a more profound effect observed in SD1068 that showed a significant reduction in indole-3-acetic acid (IAA) and a significant increase in cytokinin (CTK) at 6 days post-spray (dps). BR biosynthesis-related genes were downregulated in SD1068, but not in XLZ74. Additionally, more downregulated TFs were observed in MC-treated SD1068 than in MC-treated XLZ74, and the two varieties had very different profiles of genes involved in starch and sucrose metabolism, with those of SD1068 and XLZ74 being downregulated and upregulated by MC treatment, respectively. Together, these results indicate that although the same or similar biological pathways are affected by MC treatment in cotton varieties showing different MC sensitivity, the extent of effect is variable, leading to their different phenotypic outcomes. How the quantitative effect of MC on the biological processes associated with growth retardation is regulated is still an open question. [ABSTRACT FROM AUTHOR]

Influenza virus is an acute and highly contagious respiratory pathogen that causes great concern to public health and for which there is a need for extensive drug discovery. The small chemical compound ABMA and its analog DABMA, containing an adamantane or a dimethyl-adamantane group, respectively, have been demonstrated to inhibit multiple toxins (diphtheria toxin, Clostridium difficile toxin B, Clostridium sordellii lethal toxin) and viruses (Ebola, rabies virus, HSV-2) by acting on the host's vesicle trafficking. Here, we showed that ABMA and DABMA have antiviral effects against both amantadine-sensitive influenza virus subtypes (H1N1 and H3N2), amantadine-resistant subtypes (H3N2), and influenza B virus with EC50 values ranging from 2.83 to 7.36 µM (ABMA) and 1.82 to 6.73 µM (DABMA), respectively. ABMA and DABMA inhibited the replication of influenza virus genomic RNA and protein synthesis by interfering with the entry stage of the virus. Molecular docking evaluation together with activity against amantadine-resistant influenza virus strains suggested that ABMA and DABMA were not acting as M2 ion channel blockers. Subsequently, we found that early internalized H1N1 virions were retained in accumulated late endosome compartments after ABMA treatment. Additionally, ABMA disrupted the early stages of the H1N1 life cycle or viral RNA synthesis by interfering with autophagy. ABMA and DABMA protected mice from an intranasal H1N1 challenge with an improved survival rate of 67%. The present study suggests that ABMA and DABMA are potential antiviral leads for the development of a host-directed treatment against influenza virus infection. [ABSTRACT FROM AUTHOR]

The Reticuloendotheliosis virus (REV) primarily causes avian severe immunosuppression, in addition to other symptoms, which include avian dwarfing syndrome and chronic tumors in lymphoid and other tissue. To date, REV's molecular mechanisms leading to immunosuppression have not been fully elucidated. In the current study, we aimed to elucidate the role of microRNAs (miRNA) in regulating gene expression during REV infections. Therefore, we used a high-dose spleen necrosis virus (SNV) model of REV to inoculate one-day-old specific pathogen-free (SPF) chickens, thereby inducing congenital infections. We analyzed miRNA and mRNA expression profiles using Next Generation Sequencing (NGS) in a total of 19 spleen samples that were collected at 7, 14, and 21 days post infection (dpi). The results showed that 63 differentially expressed miRNAs (DEmiRNAs) (30 known miRNAs and 33 novel miRNAs) and 482 differentially expressed target genes (DETGs) were identified. Integration analysis identified 886 known miRNA–mRNA and 580 novel miRNA–mRNA interaction pairs, which involved miRNAs that were inversely correlated with the above DETGs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DETGs were considerably enriched in the immune-relevant pathways category, such as immune system, cell growth and death, signaling molecules and interaction, signal transduction, etc. We further verified selected immune-relevant miRNA and their DETGs while using quantitative RT-PCR (qRT-PCR). Overall, our data revealed valuable immune-related miRNA–mRNA interaction information that occurred during REV infections, thereby broadening our understanding of the REV-induced immunosuppression. [ABSTRACT FROM AUTHOR]

Green-colored fiber (GCF) is the unique raw material for naturally colored cotton textile but we know little about the pigmentation process in GCF. Here we compared transcriptomes and metabolomes of 12, 18 and 24 days post-anthesis (DPA) fibers from a green fiber cotton accession and its white-colored fiber (WCF) near-isogenic line. We found a total of 2047 non-redundant metabolites in GCF and WCF that were enriched in 80 pathways, including those of biosynthesis of phenylpropanoid, cutin, suberin, and wax. Most metabolites, particularly sinapaldehyde, of the phenylpropanoid pathway had a higher level in GCF than in WCF, consistent with the significant up-regulation of the genes responsible for biosynthesis of those metabolites. Weighted gene co-expression network analysis (WGCNA) of genes differentially expressed between GCF and WCF was used to uncover gene-modules co-expressed or associated with the accumulation of green pigments. Of the 16 gene-modules co-expressed with fiber color or time points, the blue module associated with G24 (i.e., GCF at 24 DPA) was of particular importance because a large proportion of its genes were significantly up-regulated at 24 DPA when fiber color was visually distinguishable between GCF and WCF. A total of 56 hub genes, including the two homoeologous Gh4CL4 that could act in green pigment biosynthesis, were identified among the genes of the blue module that are mainly involved in lipid metabolism, phenylpropanoid biosynthesis, RNA transcription, signaling, and transport. Our results provide novel insights into the mechanisms underlying pigmentation of green fibers and clues for developing cottons with stable green colored fibers. [ABSTRACT FROM AUTHOR]

The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) gene editing system has been shown to be able to induce highly efficient mutagenesis in the targeted DNA of many plants, including cotton, and has become an important tool for investigation of gene function and crop improvement. Here, we developed a simple and easy to operate CRISPR/Cas9 system and demonstrated its high editing efficiency in cotton by targeting-ALARP, a gene encoding alanine-rich protein that is preferentially expressed in cotton fibers. Based on sequence analysis of the target site in the 10 transgenic cottons containing CRISPR/Cas9, we found that the mutation frequencies of GhALARP-A and GhALARP-D target sites were 71.4–100% and 92.9–100%, respectively. The most common editing event was deletion, but deletion together with large insertion was also observed. Mosaic mutation editing events were detected in most transgenic plants. No off-target mutation event was detected in any the 15 predicted sites analyzed. This study provided mutants for further study of the function of GhALARP in cotton fiber development. Our results further demonstrated the feasibility of use of CRISPR/Cas9 as a targeted mutagenesis tool in cotton, and provided an efficient tool for targeted mutagenesis and functional genomics in cotton. [ABSTRACT FROM AUTHOR]