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Background: Incubation behaviour, an instinct for natural breeding in poultry, is strictly controlled by the central nervous system and multiple neuroendocrine hormones and neurotransmitters, and is closely associated with the cessation of egg laying. Therefore, it is essential for the commercial poultry industry to clarify the molecular regulation mechanism of incubation behaviour. Here, we used high-throughput sequencing technology to examine the pituitary transcriptome of Changshun green-shell laying hen, a local breed from Guizhou province, China, with strong broodiness, in two reproductive stages, including egg-laying phase (LP) and incubation phase (BP). We also analyze the differences in gene expression during the transition from egg-laying to incubation, and identify critical pathways and candidate genes involved in controlling the incubation behaviour in the pituitary. Results: In this study, we demonstrated that a total of 2089 differently expressed genes (DEGs) were identified in the pituitary, including 842 up-regulated and 1247 down-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that steroid biosynthesis pathway and neuroactive ligand-receptor interaction were significantly enriched based on DEGs commonly identified in pituitary. Further analysis revealed that SRC, ITGB4, ITGB3, PIK3R3 and DRD2 may play crucial roles in the regulation of incubation behaviour. Conclusions: We identified 2089 DEGs and the key signaling pathways which may be closely correlated with incubation in Changshun green-shell laying hens, and clarified the molecular regulation mechanism of incubation behaviour. Our results indicate the complexity and variety of differences in reproductive behaviour of different chicken breeds. [ABSTRACT FROM AUTHOR]

Circadian dysfunction is a common non-motor symptom in Parkinson's disease (PD). The potential influence of aggravated α-synuclein (SNCA) on circadian disruption remains unclear. SNCAA53T-overexpressing transgenic mice (SNCAA53T mice) and wild-type (WT) littermates were used in this study. The energy metabolism cage test showed differences in 24-h activity pattern between SNCAA53T and WT mice. When compared with the age-matched littermates, brain and muscle ARNT-like 1 (BMAL1) was downregulated in SNCAA53T mice. BMAL1 was downregulated in PC12 cells overexpressing SNCA. Degradation of BMAL1 protein remained unchanged after overexpression of SNCA, while its mRNA level decreased. miRNA (miR)-155 was upregulated by overexpression of SNCA, and downregulation of BMAL1 was partially reversed by transfection with miR-155 inhibitor. Our findings demonstrated that overexpression of SNCA induced biorhythm disruption and downregulated BMAL1 expression through decreasing stability of BMAL1 mRNA via miR-155. [ABSTRACT FROM AUTHOR]

Background: Previous studies have pointed out that sevoflurane (Sef) preconditioning could relieve myocardial ischemia/reperfusion (I/R) injury, but the mechanisms is still unknown. Methods: C57BL/6 mice model of myocardial I/R injury was established to evaluate the function of Sef. Briefly, Sef was inhaled before I/R operation. The levels of TIMP3, oxidative damage-related factors, and mitogen activated protein kinases (MAPKs) pathway-related factors were measured by qRT-PCR and western blot. Myocardial infarction (MI) area was detected by triphenyl tetrazolium chloride (TTC) staining assay. Results: Sef preconditioning reduced MI area in myocardial I/R injury mice and upregulated TIMP3 expression in myocardial tissues of I/R mice. In addition, downregulation of TIMP3 reversed the alleviating effects of Sef pretreatment on myocardial oxidative damage and inhibited the effect of Sef pretreatment on MAPKs pathway activity. Conclusion: Sef preconditioning ameliorated myocardial I/R injury by modulating MAPKs pathway activity via upregulating TIMP3. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs (18∼ 25 nt in length) that act as master regulators of eukaryotic gene expression. They might play an oncogenic or tumor-suppressive role in multiple cancers. In recent decades, several studies have focused on the functions and mechanisms of miR-335 in cancer. The expression level of miR-335 in tissues and cells varies with cancer types, and miR-335 has been proposed as a potential biomarker for the prognosis of cancer. Besides, miR-335 may serve as an oncogene or tumor suppressor via regulating different targets or pathways in tumor initiation, development, and metastasis. Furthermore, miR-335 also influences tumor microenvironment and drug sensitivity. MiR-335 is regulated by various factors such as lncRNAs and microRNAs. In this review, we reveal the functions and targets of miR-335 in various cancers and its potential application as a possible biomarker in prognostic judgment and treatment of malignant tumors. [ABSTRACT FROM AUTHOR]

In order to define translocation characteristics of 13C-photoassimilates to fruit during the fruit development stage in 'Fuji' apple, the 13C labeled tracer method was used in whole five-year-old 'Fuji'3/M26/ Malus hupehensis (Pamp.) Rehder apple trees at different days after flowering (DAF). The changes in 13C translocation to the fruit, source strength of the leaves, and sink strength of the fruits were assessed. The results indicated that the δ13C value and 13C distribution rate of the fruit increased first and then decreased with the increase in the fruit development period, being higher from 120 to 135 DAF. The leaves appeared to moderately senesce in an attempt to maintain high photosynthesis during 120–135 DAF, which promoted the outward transport of photoassimilates. The single fruit weight and longitudinal and transverse diameter of the fruit increased rapidly during 120–150 DAF, which increased the sink zone for the unloading of photoassimilates in the fruit. The activity of sorbitol dehydrogenase (SDH) and amylase (AM), the content of indole-3-acetic acid (IAA), the gibberellin (GA 3) and abscisic acid (ABA) in the fruit flesh, and the gene expression levels of MdSOT1 , MdSOT2 , MdSOT3 , MdSUT1 , and MdSUT4 in the fruit stalk tissue were higher during 120–135 DAF. At this point, the difference in the sorbitol content between the fruit stalk and fruit flesh was also at the highest level of the entire year. These factors together increased the sink activity of the fruit, thus improving the photoassimilate transport efficiency to the fruit. • Higher 13C-photoassimilates was transported to fruit during 120–135 DAF. • P n was strong and leaf appeared to moderately senescence during 120–135 DAF. • Sink zone and sink activity of fruit were the higher during 120–135 DAF. [ABSTRACT FROM AUTHOR]

In order to improve the problem of poor coloring caused by high fruit nitrogen in apple production, we studied the effects of different concentrations of abscisic acid (ABA: 0, 50, 100, and 150 mg/L) and fluridone (ABA biosynthesis inhibitor) on the fruit of 'Red Fuji' apple (Malus Domestica Borkh.) in the late stage of apple development (135 days after blooming) in 2017 and 2018. The effects of these treatments on the distribution of 13C and 15N and anthocyanin synthesis in fruit were studied. The results showed that the expression levels of ABA synthesis and receptor genes in the peel and flesh were upregulated by exogenous ABA treatment. An appropriate concentration of ABA significantly increased the expression of anthocyanin synthesis genes and transcription factors and increased the content of anthocyanin in the peel. The results of 13C and 15N double isotope labeling showed that exogenous ABA coordinated the carbon–nitrogen nutrient of apple fruit in the late stage of the development, reduced the accumulation of fruit nitrogen, increased the accumulation of fruit carbon and sugar, provided a substrate for anthocyanin synthesis, or promoted anthocyanin synthesis through the sugar signal regulation mechanism. Comprehensive analysis showed that the application of 100 mg/L ABA effectively improved the problem of poor coloring caused by high fruit nitrogen in the late stage of apple development and is beneficial to the accumulation of carbon in fruit and the formation of color. [ABSTRACT FROM AUTHOR]

With the broad application of high-throughput sequencing, more whole-genome resequencing data and de novo assemblies of natural populations are becoming available. For a particular species, in general, only the reference genome is well established and annotated. Computational tools based on sequence alignment have been developed to investigate the gene models of individuals belonging to the same or closely related species. During this process, inconsistent alignment often obscures genome annotation lift over and leads to improper functional impact prediction for a genomic variant, especially in plant species. Here, we proposed the zebraic striped dynamic programming algorithm, which provides different weights to genetic features to refine genome annotation lift over. Testing of our zebraic striped dynamic programming algorithm on both plant and animal genomic data showed complementation to standard sequence approach for highly diverse individuals. Using the lift over genome annotation as anchors, a base-pair resolution genome-wide sequence alignment and variant calling pipeline for de novo assembly has been implemented in the GEAN software. GEAN could be used to compare haplotype diversity, refine the genetic variant functional annotation, annotate de novo assembly genome sequence, detect homologous syntenic blocks, improve the quantification of gene expression levels using RNA-seq data, and unify genomic variants for population genetic analysis. We expect that GEAN will be a standard tool for the coming of age of de novo assembly population genetics. [ABSTRACT FROM AUTHOR]

The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development. [ABSTRACT FROM AUTHOR]

Corynebacterium glutamicum (C. glutamicum) is a favorable host cell for the production of recombinant proteins, such as important enzymes and pharmaceutical proteins, due to its excellent potential advantages. Herein, we sought to systematically explore the influence of recombinant protein expression on the transcription and metabolism of C. glutamicum. Two C. glutamicum strains, the wild-type strain and an engineered strain expressing enhanced green fluorescent protein (EGFP), were cultured in parallel in 5-L bioreactors to study the change in metabolism in the process of EGFP expression. The results revealed that EGFP expression had great effects on the growth and metabolism of C. glutamicum and contributed to metabolism-like anaerobic conditions as follows: glycolysis was enhanced, the TCA cycle was shunted, and Glu, Val, Met, lactate and acetate were accumulated to produce sufficient ATP for EGFP production and transfer. Many differentially expressed genes related to ribosomal protein, transcriptional regulators, and energy metabolism were found to be expressed in the presence of EGFP, laying the foundation for identifying genomic loci to change the flow of the host cell metabolism to improve the ability of expressing foreign proteins in C. glutamicum. [ABSTRACT FROM AUTHOR]

Cervical cancer is the most common cause of cancer-related deaths in women from developing countries. Identification of novel prognostic predictors or therapeutic targets may improve patient prognosis. In the current study, we demonstrated by real-time PCR that miR-224 expression was significantly upregulated (1.82-fold, P = 0.0025) in cervical cancer tissues (n = 126) compared with in normal cervical tissues (n = 64). Higher expression of miR-224 was significantly associated with poorer prognostic factors, including advanced FIGO stage, nodal metastasis, larger tumor size, vascular involvement and deep stromal invasion (all P < 0.05). Enforced expression of miR-224 promoted cell proliferation, migration and invasion in SiHa and CaSki cancer cell lines. Bioinformatic analysis indicated that RASSF8 (RAS-association domain family 8) was a potential target of miR-224. Western blot analysis and luciferase reporter assay showed that overexpressed miR-224 inhibited RASSF8 protein expression and decreased the activity of a luciferase reporter containing the 3′ untranslated region (UTR) of RASSF8, respectively. Further, RASSF8 knockdown by specific RNAi showed similar effects in cervical cancer cells transfected with miR-224 mimic. Our findings suggest that miR-224 directly targets RASSF8 and thereby acts as a tumor promoter in cervical cancer progression. [ABSTRACT FROM AUTHOR]

Background/Aims: Golgi phosphoprotein 3 (GOLPH3) is a newly reported oncogene that plays a significant role in regulating cell growth. Recent research has shown that overexpression of GOLPH3 is correlated with patient survival and M classification in breast cancer and other cancers. However, the mechanisms by which GOLPH3 contributes to metastasis in non-small cell lung cancer (NSCLC) have not been previously clarified and are therefore the focus of this work. Methods: Immunohistochemistry (IHC) and western blotting analysis were performed to assess the GOLPH3 protein level, small interfering RNA (siRNA) and transwell assays were conducted to investigate the role of GOLPH3 in migration and invasion, and real-time PCR was performed to estimate the level of GOLPH3 mRNA expression. Results: GOLPH3 was significantly correlated with clinicopathological variables, such as the clinical stage (P=0.012), T classification (P=0.002) and metastasis (M classification) (P=0.008), in NSCLC patients and was negatively correlated with the prognosis. Knockdown of GOLPH3 significantly suppressed the migratory and invasive ability of NSCLC cell lines and downregulated the enzyme activity and protein levels of MMP-2 and MMP-9. Conclusions: The expression level of GOLPH3 is correlated with metastasis and prognosis in NSCLC, and GOLPH3 mediates metastasis by regulating the protein levels of MMP-2 and MMP-9 in vitro. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Context: DTD is a Chinese herb prescription used for centuries to treat atherosclerosis or dizziness. Previous studies show that DTD could inhibit ICAM-1 expression induced by TNF-α. However, its mechanism has never been clearly described. Objective: To examine the hypothesis that DTD might inhibit TNF-α-induced ICAM-1 expression through regulating the expression of p53 and p21. Materials and methods: The rats were orally treated with DTD for 3 d (2.3 g/kg per day), and then the serum was collected. HUVECs were cultured and stimulated by TNF-α with or without DTD serum (5, 10, and 20%). The expression of ICAM-1 mRNA was examined by RT-PCR and the expression of p53 and p21 was examined by western blot analysis. Results: The ICAM-1 mRNA levels induced by TNF-α were significantly reduced from 23 to 47%, and the expression of p53 and p21 mRNA levels were significantly reduced from 13 to 43% and 14 to 42%, as the concentration of DTD serum increased. In western blot, TNF-α-induced the expression of p53 and was inhibited from 15 to 53%, by DTD serum in a concentration-dependent manner. TNF-α-induced expression of p21 was inhibited from 2 to 37%, by DTD serum in a concentration-dependent manner. Discussion and conclusion: DTD has a function of 'dissolving phlegm', thus it is chosen for the treatment of atherosclerosis. This study demonstrated that DTD could significantly inhibit the expression of ICAM-1, p53 and p21, which are important factors of atherosclerosis. Therefore, the present study indicates the pharmacological basis for treatment of atherosclerosis with DTD. [ABSTRACT FROM AUTHOR]

Jun is a highly conserved member of the multimeric activator protein 1 transcription factor complex and plays an important role in human cancer where it is known to be critical for proliferation, cell cycle regulation, differentiation, and cell death. All of these biological functions are also crucial for embryonic development. Although all Jun null mouse embryos die at mid-gestation with persistent truncus arteriosus, a severe cardiac outflow tract defect also seen in human congenital heart disease, the developmental mechanisms are poorly understood. Here we show that murine Jun is expressed in a restricted pattern in several cell populations important for cardiovascular development, including the second heart field, pharyngeal endoderm, outflow tract and atrioventricular endocardial cushions and post-migratory neural crest derivatives. Several genes, including Isl1, molecularly mark the second heart field. Isl1 lineages include myocardium, smooth muscle, neural crest, endocardium, and endothelium. We demonstrate that conditional knockout mouse embryos lacking Jun in Isl1-expressing progenitors display ventricular septal defects, double outlet right ventricle, semilunar valve hyperplasia and aortic arch artery patterning defects. In contrast, we show that conditional deletion of Jun in Tie2-expressing endothelial and endocardial precursors does not result in aortic arch artery patterning defects or embryonic death, but does result in ventricular septal defects and a low incidence of semilunar valve defects, atrioventricular valve defects and double outlet right ventricle. Our results demonstrate that Jun is required in Isl1-expressing progenitors and, to a lesser extent, in endothelial cells and endothelial-derived endocardium for cardiovascular development but is dispensable in both cell types for embryonic survival. These data provide a cellular framework for understanding the role of Jun in the pathogenesis of congenital heart disease. [ABSTRACT FROM AUTHOR]

Summary: Maintenance of normal endothelial function is critical to various aspects of blood vessel function, but its regulation is poorly understood. In this study, we show that disruption of baseline fibroblast growth factor (FGF) signaling to the endothelium leads to a dramatic reduction in let-7 miRNA levels that, in turn, increases expression of transforming growth factor (TGF)-β ligands and receptors and activation of TGF-β signaling, leading to endothelial-to-mesenchymal transition (Endo-MT). We also find that Endo-MT is an important driver of neointima formation in a murine transplant arteriopathy model and in rejection of human transplant lesions. The decline in endothelial FGF signaling input is due to the appearance of an FGF resistance state that is characterized by inflammation-dependent reduction in expression and activation of key components of the FGF signaling cascade. These results establish FGF signaling as a critical factor in maintenance of endothelial homeostasis and point to an unexpected role of Endo-MT in vascular pathology. [Copyright &y& Elsevier]

Summary [ABSTRACT FROM AUTHOR]

Abstract: Neuromedin U (NMU) has recently been reported to play a role in nociception. However, to date, the relevant mechanisms still remain unknown. In the present study, we investigated the expression profile of NMU receptors in mouse dorsal root ganglia (DRG) and identified a novel functional role of NMU in modulating T-type Ca2+ channel currents (T-currents) as well as membrane excitability in small DRG neurons. We found that NMU inhibited T-currents in a dose-dependent manner in mouse small DRG neurons that endogenously expressed NMU type 1 (NMUR1), but not NMUR2 receptors. NMU (1μM) reversibly inhibited T-currents by ∼27.4%. This inhibitory effect was blocked by GDP-β-S or pertussis toxin (PTX), indicating the involvement of a Gi/oα-protein. Using depolarizing prepulse or intracellular application of QEHA, a synthetic peptide which competitively blocks G-protein βγ subunit (Gβγ) mediated signaling, we found the absence of functional coupling between Gβγ and T-type Ca2+ channels. Pretreatment of the cells with H89, a protein kinase A (PKA) inhibitor, or intracellular application of PKI 5-24, blocked NMU-induced T-current inhibition, whereas inhibition of phospholipase C or protein kinase C elicited no such effects. In addition, we observed a significant decreased firing frequency of action potentials of small DRG neurons induced by NMU, which could be abrogated by pretreatment of the cells with NiCl2 (100μM). Taken together, these results suggested that NMU inhibits T-currents via PTX-sensitive PKA pathway, which might contribute to its physiological functions including neuronal hypoexcitability in small DRG neurons in mice. [Copyright &y& Elsevier]

Simple Summary: Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and high mortality rate, with complex molecular alterations, including glycosylation. O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic modification process jointly controlled by the "writer" O-GlcNAc transferase (OGT) and "eraser" O-GlcNAcase (OGA), and an increase in total O-GlcNAc correlates with advanced malignant HCC phenotypes. The aim of our study was to explore the potential regulatory patterns underlying the OGT/OGA imbalance that contributes to HCC malignancies. We confirmed that RANBP2, one of the SUMO E3 ligases, downregulates OGA transcription while not affecting OGT. As a transcriptional factor positively regulating OGA, CEBPα was also SUMOylated and destabilized by RANBP2. Our in vitro and in vivo studies provide evidence of RANBP2 downregulating OGA and thus triggering O-GlcNAcylation in a CEBPα-dependent manner. The subsequent hyper-O-GlcNAcylation of protein substrates such as PGC1α via the RANBP2–CEBPα–OGA pathway may represent a pharmaceutical strategy for HCC treatment. O-GlcNAcylation is an important post-translational modification (PTM) jointly controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Aberrant hyper-O-GlcNAcylation is reported to yield hepatocellular carcinoma (HCC) malignancy, but the underlying mechanisms of the OGT/OGA imbalance responsible for HCC tumorigenesis remain largely unknown. Here, we report that RAN-binding protein 2 (RANBP2), one of the small ubiquitin-like modifier (SUMO) E3 ligases, contributed to malignant phenotypes in HCC. RANBP2 was found to facilitate CCAAT/enhancer-binding protein alpha (CEBPα) SUMOylation and degradation by direct interplay with CEBPα. As a transcriptional factor, CEBPα was verified to augment OGA transcription, and further experiments demonstrated that RANBP2 enhanced the O-GlcNAc level by downregulating OGA transcription while not affecting OGT expression. Importantly, we provided in vitro and in vivo evidence of HCC malignant phenotypes that RANBP2 triggered through an imbalance of OGT/OGA and subsequent higher O-GlcNAcylation events for oncogenic proteins such as peroxisome proliferative-activated receptor gamma coactivator 1 alpha (PGC1α) in a CEBPα-dependent manner. Altogether, our results show a novel molecular mechanism whereby RANBP2 regulates its function through CEBPα-dependent OGA downregulation to induce a global change in the hyper-O-GlcNAcylation of genes, such as PGC1α, encouraging the further study of promising implications for HCC therapy. [ABSTRACT FROM AUTHOR]

• Using Nanopore sequencing read to quantify tea gene expression is repeatable. • RNA abundance measured using Nanopore, Illumina, and qRT-PCR are consistent. • Differentially expressed genes investigated using Nanopore and Illumina are similar. • Nanopore long RNA read could refine gene structure. Transcriptome profiles have been widely captured using short-read sequencing technology, but there are still limitations partially due to the read length. Here, we generated long reads using Oxford Nanopore PromethION™ technology and short reads using the Illumina sequencing platform to study the transcriptome of root, stem, and leaf of Camellia sinensis cv. Fudingdabai. We mapped the Nanopore reads to the Shuchazao of C. sinensis genome sequence, and the mapping rates ranged from 82.63% to 90.59% (average 86.44%); this is lower than that of the Illumina reads which was 87.83% to 91.14% (average 90.12%). Gene expression level was quantified using the Nanopore and Illumina data and we observed a good agreement. The same tea leaf flavor synthesis pathways were highlighted using both sequencing technologies when analyzing the differentially expressed genes between leaf and root. Alternative splicing was then analyzed, and the intron-retention was observed as the most common alternative splicing. Moreover Nanopore long reads could correct transcript isoform annotation for differential expression investigation purposes. Nanopore sequencing techniques can provide a novel reference basis for molecular analysis of tea plants. [ABSTRACT FROM AUTHOR]

Tet-mediated DNA demethylation plays an important role in shaping the epigenetic landscape and chromatin accessibility to control gene expression. While several studies demonstrated pivotal roles of Tet in regulating embryonic development, little is known about their functions in heart development. Here we analyze DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice. We find that cardiac-specific deletion of Tet2 and Tet3 in mice (Tet2/3-DKO) leads to ventricular non-compaction cardiomyopathy (NCC) with embryonic lethality. Single-cell RNA-seq analyses reveal a reduction in cardiomyocyte numbers and transcriptional reprogramming in cardiac tissues upon Tet2/3 depletion. Impaired DNA demethylation and reduced chromatin accessibility in Tet2/3-DKO mice further compromised Ying-yang1 (YY1) binding to its genomic targets, and perturbed high-order chromatin organization at key genes involved in heart development. Our studies provide evidence of the physiological role of Tet in regulating DNA methylation dynamics and chromatin organization during early heart development. Tet-mediated DNA demethylation is intimately involved in reguatling embryonic development. Here the authors characterise DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice and provide evidence that Tet-mediated DNA demethylation plays a role in regulating chromatin organization during early heart development. [ABSTRACT FROM AUTHOR]

Background: Chinese cordyceps, also known as Chinese caterpillar fungus (Ophiocordyceps sinensis, syn. Cordyceps sinensis), is of particular interest for its cryptic life cycle and economic and ecological importance. The large-scale artificial cultivation was succeeded recently after several decades of efforts and attempts. However, the induction of primordium, sexual development of O. sinensis and the molecular basis of its lifestyle still remain cryptic. Results: The developmental transcriptomes were analyzed for six stages covering the whole developmental process, including hyphae (HY), sclerotium (ST), primordium (PR), young fruiting body (YF), developed fruiting body (DF) and mature fruiting body (MF), with a focus on the expression of sexual development-related genes. Principal component analysis revealed that the gene expression profiles at the stages of primordium formation and fruiting body development are more similar than those of the undifferentiated HY stage. The PR and MF stages grouped together, suggesting that primordium differentiation and sexual maturation have similar expression patterns. Many more DEGs were identified between the ST and HY stages, covering 47.5% of the O. sinensis genome, followed by the comparisons between the ST and PR stages. Using pairwise comparisons and weighted gene coexpression network analysis, modules of coexpressed genes and candidate hub genes for each developmental stage were identified. The four mating type loci genes expressed during primordium differentiation and sexual maturation; however, spatiotemporal specificity of gene expression indicated that they also expressed during the anamorphic HY stage. The four mating type genes were not coordinately expressed, suggesting they may have divergent roles. The expression of the four mating type genes was highest in the fertile part and lowest in the sclerotium of the MF stage, indicating that there is tissue specificity. Half of genes related to mating signaling showed as the highest expression in the ST stage, indicating fruiting was initiated in the ST stage. Conclusions: These results provide a new perspective to understanding of the key pathways and hub genes, and sexual development-related gene profile in the development of Chinese cordyceps. It will be helpful for underlying sexual reproduction, and add new information to existing models of fruiting body development in edible fungi. [ABSTRACT FROM AUTHOR]

[Display omitted] • Exogenous AHLs improve nitrogen removal performance and genes expression levels at 15 ℃. • Amended C6-HSL and C8-HSL change the correlations between anammox bacteria and others. • C8-HSL and C6-HSL upregulate genes abundances involving amino sugar and amino acid biosynthesis pathway. In this study, C6-HSL and C8-HSL were separately introduced into anammox biofilm reactors to facilitate the anammox performance at 15 ℃. After operation 138 d, total nitrogen removal efficiencies in reactors with amendment C6-HSL or C8-HSL at 15 ℃ reached 76.2% and 74.6%, respectively. Content of extracellular polymeric substances increased by 19.8%, 67.7% and 121.2% in control group, C6-HSL and C8-HSL addition group, respectively. Genes associated with nitrogen removal (i.e., hzo , hzsB , nirS , and ccsB) showed higher expression level at amendment C6-HSL or C8-HSL group. Metagenomics analysis found that amendment of C6-HSL or C8-HL resulted in an increased abundance of genes related to the tricarboxylic acid cycle, amino sugar and nucleotide sugar metabolism, and also genes associated with amino acid biosynthesis pathways. Overall, amendment C6-HSL or C8-HSL had been confirmed as the effective method to improve the performance of anammox bioreactor at 15 ℃. [ABSTRACT FROM AUTHOR]

It has been demonstrated that acid sensing ionic channels (ASICs) are present in the central and peripheral nervous system of mammals, including the retina. However, it remains unclear whether the zebrafish retina also expresses ASICs. In the present study, the expression and distribution of zasic1 were examined in the retina of zebrafish. Both zasic1 mRNA and protein expressions were detected in the adult zebrafish retina. A wide distribution of ASIC1 in zebrafish retina was confirmed using whole mount in situ hybridization and immunohistochemistry study. Acidosis-induced currents in the isolated retinal ganglion cells (RGCs) were also recorded using whole cell patch clamping. Moreover, blockade of ASICs channel significantly reduced the locomotion of larval zebrafish in response to light exposure. In sum, our data demonstrate the presence of ASIC1 and its possible functional relevance in the retina of zebrafish. [ABSTRACT FROM AUTHOR]

Abstract: Carcinogen-DNA adducts could lead to mutations in critical genes, eventually resulting in cancer. Many studies have shown that retinoic acid (RA) plays an important role in inducing cell apoptosis. Here we have tested the hypothesis that levels of carcinogen-DNA adducts can be diminished by DNA repair and/or by eliminating damaged cells through apoptosis. Our results showed that the levels of total DNA adducts in HepG2 cells treated with benzo(a)pyrene (BP, 2μM)+RA (1μM) were significantly reduced compared to those treated with BP only (P =0.038). In order to understand the mechanism of attenuation of DNA adducts, further experiments were performed. Cells were treated with BP (4μM) for 24h to initiate DNA adduct formation, following which the medium containing BP was removed, and fresh medium containing 1μM RA was added. The cells were harvested 24h after RA treatment. Interestingly, the levels of total DNA adducts were lower in the BP/RA group (390±34) than those in the BP/DMSO group (544±33), P =0.032. Analysis of cell apoptosis showed an increase in BP+RA group, compared to BP or RA only groups. Our results also indicated that attenuation of BP-DNA adducts by RA was not primarily due to its effects on CYP1A1 expression. In conclusion, our results suggest a mechanistic link between cellular apoptosis and DNA adduct formation, phenomena that play important roles in BP-mediated carcinogenesis. Furthermore, these results help understand the mechanisms of carcinogenesis, especially in relation to the chemopreventive properties of nutritional apoptosis inducers. [Copyright &y& Elsevier]

Summary: MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression posttranscriptionally. We investigated the hypothesis that bone morphogenetic protein (Bmp) signaling regulates miRNAs in cardiac progenitor cells. Bmp2 and Bmp4 regulate OFT myocardial differentiation via regulation of the miRNA-17-92 cluster. In Bmp mutant embryos, myocardial differentiation was delayed, and multiple miRNAs encoded by miRNA-17-92 were reduced. We uncovered functional miRNA-17-92 seed sequences within the 3′ UTR of cardiac progenitor genes such as Isl1 and Tbx1. In both Bmp and miRNA-17-92 mutant embryos, Isl1 and Tbx1 expression failed to be correctly downregulated. Transfection experiments indicated that miRNA-17 and miRNA-20a directly repressed Isl1 and Tbx1. Genetic interaction studies uncovered a synergistic interaction between miRNA-17-92 cluster and Bmp4, providing direct in vivo evidence for the Bmp-miRNA-17-92 regulatory pathway. Our findings indicate that Bmp signaling directly regulates a miRNA-mediated effector mechanism that downregulates cardiac progenitor genes and enhances myocardial differentiation. [ABSTRACT FROM AUTHOR]

Abstract: Although fibroblast growth factor 9 (FGF9) is widely expressed in the central nervous system (CNS), the function of FGF9 in neural development remains undefined. To address this question, we deleted the Fgf9 gene specifically in the neural tube and demonstrated that FGF9 plays a key role in the postnatal migration of cerebellar granule neurons. Fgf9-null mice showed severe ataxia associated with disrupted Bergmann fiber scaffold formation, impaired granule neuron migration, and upset Purkinje cell maturation. Ex vivo cultured wildtype or Fgf9-null glia displayed a stellate morphology. Coculture with wildtype neurons, but not Fgf9-deficient neurons, or treating with FGF1 or FGF9 induced the cells to adopt a radial glial morphology. In situ hybridization showed that Fgf9 was expressed in neurons and immunostaining revealed that FGF9 was broadly distributed in both neurons and Bergmann glial radial fibers. Genetic analyses revealed that the FGF9 activities in cerebellar development are primarily transduced by FGF receptors 1 and 2. Furthermore, inhibition of the MAP kinase pathway, but not the PI3K/AKT pathway, abrogated the FGF activity to induce glial morphological changes, suggesting that the activity is mediated by the MAP kinase pathway. This work demonstrates that granule neurons secrete FGF9 to control formation of the Bergmann fiber scaffold, which in turn, guides their own inward migration and maturation of Purkinje cells. [Copyright &y& Elsevier]