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Histological interpretation of the rare pleomorphic xanthoastrocytoma (PXA) has been the holy grail for treatment options. However, no stand-alone clinical interventions have been developed owing to the lack of gene expression profiling data in PXA/APXA patients. We first time report the comprehensive analyses of the coding as well as long non-coding RNA (lncRNA) signatures of PXA/APXA patients. Several genes such as IGFBP2, NF1, FOS, ERBB2, and lncRNAs such as NEAT1, HOTAIRM1, and GAS5 known to play crucial roles in glioma patients were also deregulated in PXA patients suggesting the commonality in the molecular signatures. PPI network, co-expression, and lncRNA-mRNA interaction studies unraveled hub genes (such as ERBB2, FOS, RPA1) and networks that may play a critical role in PXA biology. The most enriched pathways based on gene profiles were related to TLR, chemokine, MAPK, Rb, and PI3K-Akt signaling pathways. The lncRNA targets were enriched in glucuronidation, adipogenesis, TGF-beta signaling, EGF/EGFR signaling, and cell cycle pathways. Interestingly, several mRNAs like PARVG, and ABI2 were found to be targeted by multiple lncRNAs suggesting a tight control of their levels. Some of the most prominent lncRNA-mRNA pairs were LOC728730: MRPL9, XLOC_l2_011987: ASIC2, lnc-C1QTNF5-1: RNF26. Notably, several lncRNAs such as lnc-CETP-1, lnc-XRCC3-1, lnc-RPL31-1, lnc-USP13-1, and MAPKAPK5-AS1, and genes such as RPA1, NTRK3, and CNRP1 showed strong correlation to the progression-free survival of PXA patients suggesting their potential as novel biomarkers. Overall, the findings of this study may facilitate the development of a new realm of RNA biology in PXA that may have clinical significance in the future. [ABSTRACT FROM AUTHOR]

Chlorophyll (Chl) is present in many plant organs and plays vital roles during growth and development. Degradation of Chl causes the loss of green colour that typically occurs during senescence, and fruit ripening. The present study addresses genome-wide identification and bioinformatics analyses of tomato (Solanum lycopersicum), SlSGR1 (Solyc08g080090.2.1) SlSGR2 (Solyc12g056480.1.1) and SlSGR-like (Solyc04g063240.2.1) genes. Multiple sequence alignment indicated that the three tomato SGR proteins have conserved domains. Motif, sequence, and protein structure analysis showed that SlSGR-like differentially evolved from SlSGR proteins. Co-expression analyses were performed for each SlSGR using transcriptomic data of two fruit ripening stages [mature green (MG) and ripe fruit (R)] of Ailsa Craig (AC) tomato cultivar. According to the co-expression network analyses, SlSGRs participate in sulphur homeostasis, fatty acid biosynthesis, and biological processes of plant development during ripening stages of tomato. Six common genes were identified in the merged co-expression network. Also, 38 transcription factor families (TFFs) were searched in the co-expression network. Only 13 transcription factors, belonging to seven TFFs, were found to be involved in regulation of these two genes. Of these TFFs, GRAS and GeBP had five and three members for SlSGR-like and SlSGR1 in the network. The expression profiles of SlSGR1/2 and SlSGR-like in different tissues and different fruit ripening stages showed that SlSGR1/2 are highly expressed in ripening fruits, whereas SlSGR-like is more involved in leaf maturation. Moreover, expression of SlSGR1/2 and SlSGR-like in the leaves of 'Ciko' and 'Black' tomato varieties under 200mM salt stress indicated that significant expression changes occurred in SlSGR2 suggesting that SlSGR genes may be involved in signalling responses to abiotic stress. The findings provide new insight into the functions of these genes in growth and salinity stress. [ABSTRACT FROM AUTHOR]

Drought frequency and severity are exacerbated by global climate change, which could compromise forest ecosystems. However, there have been minimal efforts to systematically investigate the genetic basis of the response to drought stress in perennial trees. Here, we implemented a systems genetics approach that combines co-expression analysis, association genetics, and expression quantitative trait nucleotide (eQTN) mapping to construct an allelic genetic regulatory network comprising four key regulators (PtoeIF-2B, PtoABF3, PtoPSB33, and PtoLHCA4) under drought stress conditions. Furthermore, Hap_01PtoeIF-2B, a superior haplotype associated with the net photosynthesis, was revealed through allelic frequency and haplotype analysis. In total, 75 candidate genes related to drought stress were identified through transcriptome analyses of five Populus cultivars (P. tremula × P. alba, P. nigra, P. simonii, P. trichocarpa, and P. tomentosa). Through association mapping, we detected 92 unique SNPs from 38 genes and 104 epistatic gene pairs that were associated with six drought-related traits by association mapping. eQTN mapping unravels drought stress-related gene loci that were significantly associated with the expression levels of candidate genes for drought stress. In summary, we have developed an integrated strategy for dissecting a complex genetic network, which facilitates an integrated population genomics approach that can assess the effects of environmental threats. [ABSTRACT FROM AUTHOR]

Starch, the major component of cereal grains, affects crop yield and quality and is widely used in food and industrial applications. The biosynthesis of maize starch is a complex process involving a series of functional enzymes. However, the sophisticated regulatory mechanisms of starch biosynthetic genes have not been fully elaborated. The basic/helix-loop-helix (bHLH) transcription factors are widely distributed in eukaryotes and participate inmany physiological processes. In this study, 202 bHLH encoding genes were identified in the maize genome by Blast method. ZmICE1 gene, which belongs to the ICE subfamily of the bHLH family, was obtained and expressed mainly in maize filling endosperm and co-expressed with 14 starch biosynthesis genes. Based on the comparative analyses across different plant species, we revealed that the gene structures and protein domains of the ICE subfamily were conserved between monocots and dicots, suggesting their functional conservation feature. Yeast activation and subcellular localization assays suggested that ZmICE1 had transcriptional activation activity and localized in the nucleus. Yeast one-hybrid assays confirmed that ZmICE1 could directly bind to the promoters of ZmSSIIa and ZmGBSSI. Transient gene expression analysis in maize endosperm revealed that ZmICE1 positively regulated the expression of ZmSSIIa, but inhibited the expression of ZmGBSSI. Our results indicated that ZmICE1 could function as a regulator of maize starch biosynthesis. [ABSTRACT FROM AUTHOR]

Cyclin B2 (CCNB2) belongs to type B cell cycle family protein, which is located on chromosome 15q22, and it binds to cyclin-dependent kinases (CDKs) to regulate their activities. In this study, 103 high-throughput datasets related to all subtypes of lung cancer (LC) and cerebral ischemic stroke (CIS) with the data of CCNB2 expression were collected. The analysis of standard mean deviation (SMD) and summary receiver operating characteristic (SROC) reflecting expression status demonstrated significant up-regulation of CCNB2 in LC and CIS (Lung adenocarcinoma: SMD = 1.40, 95%CI [0.98-1.83], SROC = 0.92, 95%CI [0.89-0.94]. Lung squamous cell carcinoma: SMD = 2.56, 95%CI [1.64-3.48]. SROC = 0.97, 95%CI [0.95-0.98]. Lung small cell carcinoma: SMD = 3.01, 95%CI [2.01-4.01]. SROC = 0.98, 95%CI [0.97-0.99]. CIS: SMD = 0.29, 95%CI [0.05-0.53], SROC = 0.68, 95%CI [0.63-0.71]). Simultaneously, protein-protein interaction (PPI) analysis indicated that CCNB2 is the hub molecule of crossed high-expressed genes in CIS and LC. Through Multiscale embedded gene coexpression network analysis (MEGENA), a gene module of CIS including 76 genes was obtained and function enrichment analysis of the CCNB2 module genes implied that CCNB2 may participate in the processes in the formation of CIS and tissue damage caused by CIS, such as "cell cycle," "protein kinase activity," and "glycosphingolipid biosynthesis." Afterward, via single-cell RNA-seq analysis, CCNB2 was found upregulated on GABAergic neurons in brain organoids as well as T cells expressing proliferative molecules in LUAD. Concurrently, the expression of CCNB2 distributed similarly to TOP2A as a module marker of cell proliferation in cell cluster. These findings can help in the field of the pathogenesis of LC-related CIS and neuron repair after CIS damage. [ABSTRACT FROM AUTHOR]

The two members of the cytoplasmic FMR1‐interacting protein family, CYFIP1 and CYFIP2, are evolutionarily conserved multifunctional proteins whose defects are associated with distinct types of brain disorders. Even with high sequence homology between CYFIP1 and CYFIP2, several lines of evidence indicate their different functions in the brain; however, the underlying mechanisms remain largely unknown. Here, we performed reciprocal immunoprecipitation experiments using CYFIP1‐2 × Myc and CYFIP2‐3 × Flag knock‐in mice and found that CYFIP1 and CYFIP2 are not significantly co‐immunoprecipitated with each other in the knock‐in brains compared with negative control wild‐type (WT) brains. Moreover, CYFIP1 and CYFIP2 showed different size distributions by size‐exclusion chromatography of WT mouse brains. Specifically, mass spectrometry‐based analysis of CYFIP1‐2 × Myc knock‐in brains identified 131 proteins in the CYFIP1 interactome. Comparison of the CYFIP1 interactome with the previously identified brain region‐ and age‐matched CYFIP2 interactome, consisting of 140 proteins, revealed only eight common proteins. Investigations using single‐cell RNA‐sequencing databases suggested non‐neuronal cell‐ and neuron‐enriched expression of Cyfip1 and Cyfip2, respectively. At the protein level, CYFIP1 was detected in both neurons and astrocytes, while CYFIP2 was detected only in neurons, suggesting the predominant expression of CYFIP1 in astrocytes. Bioinformatic characterization of the CYFIP1 interactome, and co‐expression analysis of Cyfip1 with astrocytic genes, commonly linked CYFIP1 with focal adhesion proteins. Immunocytochemical analysis and proximity ligation assay suggested partial co‐localization of CYFIP1 and focal adhesion proteins in cultured astrocytes. Together, these results suggest a CYFIP1‐specific association with astrocytic focal adhesion, which may contribute to the different brain functions and dysfunctions of CYFIP1 and CYFIP2. Cover Image for this issue: https://doi.org/10.1111/jnc.15410 [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) are widely involved in the pathogenesis of cancers. However, biological roles of lncRNAs in occurrence and progression of colorectal cancer (CRC) remain unclear. The current study aimed to evaluate the expression pattern of lncRNAs and messenger RNAs (mRNAs).Methods: RNA sequencing (RNA-Seq) in CRC tissues and adjacent normal tissues from 6 CRC patients was performed and functional lncRNA-mRNA co-expression network was constructed afterwards. Gene enrichment analysis was demonstrated using DAVID 6.8 tool. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to validate the expression pattern of differentially expressed lncRNAs. Pearson correlation analysis was applied to evaluate the relationships between selected lncRNAs and mRNAs.Results: One thousand seven hundred and sixteenth differentially expressed mRNAs and 311 differentially expressed lncRNAs were screened out. Among these, 568 mRNAs were up-regulated while 1148 mRNAs down-regulated, similarly 125 lncRNAs were up-regulated and 186 lncRNAs down-regulated. In addition, 1448 lncRNA-mRNA co-expression pairs were screened out from 940,905 candidate lncRNA-mRNA pairs. Gene enrichment analysis revealed that these lncRNA-related mRNAs are associated with cell adhesion, collagen adhesion, cell differentiation, and mainly enriched in ECM-receptor interaction and PI3K-Akt signaling pathways. Finally, RT-qPCR results verified the expression pattern of lncRNAs, as well as the relationships between lncRNAs and mRNAs in 60 pairs of CRC tissues.Conclusions: In conclusion, these results of the RNA-seq and bioinformatic analysis strongly suggested that the dysregulation of lncRNA is involved in the complicated process of CRC development, and providing important insight regarding the lncRNAs involved in CRC. [ABSTRACT FROM AUTHOR]

The mitogen-activated protein kinase (MAPK) cascade is a highly conserved signal transduction pathway, ubiquitous in eukaryotes, such as animals and plants. The MAPK cascade has a dominant role in regulating plant adaptation to the environment, such as through stress responses, osmotic adjustment, and processes that modulate pathogenicity. In the present study, the MAPK cascade gene family was identified in Fagopyrum tataricum (Tartary buckwheat), based on complete genome sequence data. Using phylogenetic tree, conservative motif, and chromosome location analyses, a total of 65 FtMAPK cascade genes, distributed on five chromosomes, were classified into three families: MAPK (n = 8), MAPKK (n = 1), and MAPKKK (n = 56). Transcriptome data from Tartary buckwheat seedlings grown under different light conditions demonstrated that, under blue and red light, the expression levels of 18 and 36 FtMAPK cascade genes were up-regulated and down-regulated, respectively. Through qRT-PCR experiments, it was observed that FtMAPK5, FtMAPKK1, FtMAPKKK8, FtMAPKKK10, and FtMAPKKK24 gene expression levels in the Tartary buckwheat seedlings increased under three types of abiotic stress: drought, salt, and high temperature. A co-expression network of FtMAPK cascade genes was constructed, based on gene expression levels under different light conditions, and co-expressed genes annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, which identified numerous transcription factors related to plant abiotic stress. The authors conclude that FtMAPK cascade genes have important roles in the growth and development of Tartary buckwheat, as well as its responses to abiotic stress. [ABSTRACT FROM AUTHOR]

As one of the most important vegetable crops in the world, the production of tomatoes was restricted by salt stress. Therefore, it is of great interest to analyze the salt stress tolerance genes. As the non-coding RNAs (ncRNAs) with a length of more than 200 nucleotides, long non-coding RNAs (lncRNAs) lack the ability of protein-coding, but they can play crucial roles in plant development and response to abiotic stresses by regulating gene expression. Nevertheless, there are few studies on the roles of saltinduced lncRNAs in tomatoes. Therefore, we selected wild tomato Solanum pennellii (S. pennellii) and cultivated tomato M82 to be materials. By high-throughput sequencing, 1,044 putative lncRNAs were identified here. Among them, 154 and 137 lncRNAs were differentially expressed in M82 and S. pennellii, respectively. Through functional analysis of target genes of differentially expressed lncRNAs (DE-lncRNAs), some genes were found to respond positively to salt stress by participating in abscisic acid (ABA) signaling pathway, brassinosteroid (BR) signaling pathway, ethylene (ETH) signaling pathway, and anti-oxidation process. We also construct a salt-induced lncRNA-mRNA co-expression network to dissect the putative mechanisms of high salt tolerance in S. pennellii. We analyze the function of salt-induced lncRNAs in tomato roots at the genome-wide levels for the first time. These results will contribute to understanding the molecular mechanisms of salt tolerance in tomatoes from the perspective of lncRNAs. [ABSTRACT FROM AUTHOR]

SUMMARY: Serine carboxypeptidase‐like acyltransferases (SCPL‐ATs) play a vital role in the diversification of plant metabolites. Galloylated flavan‐3‐ols highly accumulate in tea (Camellia sinensis), grape (Vitis vinifera), and persimmon (Diospyros kaki). To date, the biosynthetic mechanism of these compounds remains unknown. Herein, we report that two SCPL‐AT paralogs are involved in galloylation of flavan‐3‐ols: CsSCPL4, which contains the conserved catalytic triad S‐D‐H, and CsSCPL5, which has the alternative triad T‐D‐Y. Integrated data from transgenic plants, recombinant enzymes, and gene mutations showed that CsSCPL4 is a catalytic acyltransferase, while CsSCPL5 is a non‐catalytic companion paralog (NCCP). Co‐expression of CsSCPL4 and CsSCPL5 is likely responsible for the galloylation. Furthermore, pull‐down and co‐immunoprecipitation assays showed that CsSCPL4 and CsSCPL5 interact, increasing protein stability and promoting post‐translational processing. Moreover, phylogenetic analyses revealed that their homologs co‐exist in galloylated flavan‐3‐ol‐ or hydrolyzable tannin‐rich plant species. Enzymatic assays further revealed the necessity of co‐expression of those homologs for acyltransferase activity. Evolution analysis revealed that the mutations of the CsSCPL5 catalytic residues may have taken place about 10 million years ago. These findings show that the co‐expression of SCPL‐ATs and their NCCPs contributes to the acylation of flavan‐3‐ols in the plant kingdom. [ABSTRACT FROM AUTHOR]

Background: The brown planthopper (BPH), Nilaparvata lugens (Stal), is a very destructive pest that poses a major threat to rice plants worldwide. BPH and rice have developed complex feeding and defense strategies in the long-term co-evolution. Methods: To explore the molecular mechanism of BPH's adaptation to resistant rice varieties, the lncRNA expression profiles of two virulent BPH populations were analyzed. The RNA-seq method was used to obtain the lncRNA expression data in TN1 and YHY15. Results: In total, 3,112 highly reliable lncRNAs in TN1 and YHY15 were identified. Compared to the expression profiles between TN1 and YHY15, 157 differentially expressed lncRNAs, and 675 differentially expressed mRNAs were identified. Further analysis of the possible regulation relationships between differentially expressed lncRNAs and differentially expressed mRNAs, identified three pair antisense targets, nine pair cis-regulation targets, and 3,972 pair co-expressed targets. Function enriched found arginine and proline metabolism, glutathione metabolism, and carbon metabolism categories may significantly affect the adaptability in BPH when it is exposed to susceptible and resistant rice varieties. Altogether, it provided scientific data for the study of lncRNA regulation of brown planthopper resistance to rice. These results are helpful in the development of new control strategies for host defense against BPH and breeding rice for high yield. [ABSTRACT FROM AUTHOR]

Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is a typical single-layer capsid dsRNA virus belonging to the Reoviridae family of the Cypovirus genus. Previous studies have shown that the BmCPV major capsid shell protein (CSP) has the ability to self-assemble into virus-like particles (VLPs), and cryo-electron microscopy of the BmCPV virions has revealed a tight mutual binding region between CSP and another capsid protein known as the Large Protrusion Protein (LPP), which further stabilizes the capsid shell. In this study, the multi-gene baculovirus expression system, Ac-MultiBac, was used to produce both solely CSP-based and CSP-LPP co-assembled VLPs. Transmission electron microscopy (TEM) results showed that addition of LPP did not affect the assembly of VLPs resulting in almost identical structure in both cases. However, ex vivo administration of VLPs to silkworm midgut tissue showed that CSP-based VLPs did not induce a significant transcriptional response in the innate immunity and RNAi gene cascades, compared to the co -assembled CSP-LPP based VLPs and the natural BmCPV virions isolated from polyhedra. The experimental results indicate that CSP and LPP attach tightly ("Plug and Display" model with CSP acting as "catcher" and LPP as "tag") to form VLPs that have a structure similar to that of the native CPV virions. Moreover, our results showed that the formation of VLPs with the two BmCPV capsid proteins is feasible, which can form the basis for the production of BmCPV-based VLPs as a new type of biological material to display exogenous proteins. [ABSTRACT FROM AUTHOR]

The mitogen-activated protein kinase (MAPK) cascade is a highly conserved signal transduction pathway, ubiquitous in eukaryotes, such as animals and plants. The MAPK cascade has a dominant role in regulating plant adaptation to the environment, such as through stress responses, osmotic adjustment, and processes that modulate pathogenicity. In the present study, the MAPK cascade gene family was identified in Fagopyrum tataricum (Tartary buckwheat), based on complete genome sequence data. Using phylogenetic tree, conservative motif, and chromosome location analyses, a total of 65 FtMAPK cascade genes, distributed on five chromosomes, were classified into three families: MAPK (n = 8), MAPKK (n = 1), and MAPKKK (n = 56). Transcriptome data from Tartary buckwheat seedlings grown under different light conditions demonstrated that, under blue and red light, the expression levels of 18 and 36 FtMAPK cascade genes were up-regulated and down-regulated, respectively. Through qRT-PCR experiments, it was observed that FtMAPK5, FtMAPKK1, FtMAPKKK8, FtMAPKKK10, and FtMAPKKK24 gene expression levels in the Tartary buckwheat seedlings increased under three types of abiotic stress: drought, salt, and high temperature. A co-expression network of FtMAPK cascade genes was constructed, based on gene expression levels under different light conditions, and co-expressed genes annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, which identified numerous transcription factors related to plant abiotic stress. The authors conclude that FtMAPK cascade genes have important roles in the growth and development of Tartary buckwheat, as well as its responses to abiotic stress. [ABSTRACT FROM AUTHOR]

Brassica species include important oil crops and vegetables in the world. The R2R3-MYB gene participates in a variety of plant functions, including the activation or inhibition of anthocyanin biosynthesis. Although previous studies have reported its phylogenetic relationships, gene structures, and expression patterns in Arabidopsis, the number and sequence variation of this gene family in Brassica crops and its involvement in the natural quantitative variation in anthocyanin biosynthesis regulation are still largely unknown. In this study, by using whole genome sequences and comprehensive genome-wide comparative analysis among the six cultivated Brassica species, 2120 R2R3-MYB genes were identified in six Brassica species, in total These R2R3-MYB genes were phylogenetically clustered into 12 groups. The R2R3-MYB family between A and C subgenomes showed better collinearity than between B and C and between A and B. From comparing transcriptional changes of five Brassica species with the purple and green leaves for the detection of the R2R3-MYB genes associated with anthocyanin biosynthesis, 7 R2R3-MYB genes were co-differentially expressed. The promoter and structure analysis of these genes showed that some variations between non-coding region, but they were highly conserved at the protein level and spatial structure. Co-expression analysis of anthocyanin-related genes and R2R3-MYBs indicated that MYB90 was strongly co-expressed with TT8, and they were co-expressed with structural genes F3H, LDOX, ANS and UF3GT at the same time. These results further clarified the roles of the R2R3-MYBs for leaf coloration in Brasica species, which provided new insights into the functions of the R2R3-MYB gene family in Brasica species. [ABSTRACT FROM AUTHOR]

Background: Nitrogen (N) is a major element and fundamental constituent of grain yield. N fertilizer plays an essential role in the roots, shoots, and leaves of crop plants. Here, we obtained two N-sensitive potato cultivars. Results: The plants were cultivated in the pots using N-deficient and N-sufficient conditions. Crop height, leaf chlorophyll content, dry matter, and N-accumulation significantly decreased under N-deficient conditions. Furthermore, we performed a comprehensive analysis of the phenotype and transcriptome, GO terms, and KEGG pathways. We used WGCNA of co-expressed genes, and 116 differentially expressed hub genes involved in photosynthesis, nitrogen metabolism, and secondary metabolites to generate 23 modules. Among those modules, six NRT gene families, four pigment genes, two auxin-related genes, and two energy-related genes were selected for qRT-PCR validation. Conclusions: Overall, our study demonstrates the co-expressed genes and potential pathways associated with N transport and accumulation in potato cultivars' roots, shoots, and leaves under N-deficient conditions. Therefore, this study provides new ideas to conduct further research on improving nitrogen use efficiency in potatoes. [ABSTRACT FROM AUTHOR]

Intracellular immune receptor nucleotide‐binding leucine‐rich repeats (NLRs) are highly regulated transcriptionally and post‐transcriptionally for balanced plant defense and growth. NLR genes often exist in gene clusters and are usually co‐expressed under various conditions. Despite intensive studies of the regulation of NLR proteins, cis‐acting elements for NLR gene induction, repression or co‐expression are largely unknown due to a larger than usual cis‐region for their expression regulation. Here we used the CRISPR/Cas9 genome editing technology to generate a series of in situ deletions at the endogenous location of an NLR gene SNC1 residing in the RPP5 gene cluster. These deletions that made in the wild type and the SNC1 constitutive expressing autoimmune mutant bon1 revealed both positive and negative cis‐acting elements for SNC1 expression. Two transcription factors that could bind to these elements were found to have an impact on the expression of SNC1. In addition, co‐expression of two genes with SNC1 in the same cluster is found to be mostly dependent on the SNC1 function. Therefore, SNC1 expression is under complex local regulation involving multiple cis‐elements and SNC1 itself is a critical regulator of gene expression of other NLR genes in the same gene cluster. [ABSTRACT FROM AUTHOR]

The beef fatty acid (FA) profile has the potential to impact human health, and displays polygenic and complex features. This study aimed to identify the transcriptomic FA profile in the longissimus thoracis muscle in Nellore beef cattle finished in feedlot. Forty‐four young bulls were sampled to assess the beef FA profile by considering 14 phenotypes and including differentially expressed genes (DEG), co‐expressed (COE), and differentially co‐expressed genes (DCO) analyses. All samples (n = 44) were used for COE analysis, whereas 30 samples with extreme phenotypes for the beef FA profile were used for DEG and DCO. A total of 912 DEG were identified, and the polyunsaturated (n = 563) and unsaturated ω‐3 (n = 346) FA sums groups were the most frequently observed. The COE analyses identified three modules, of which the blue module (n = 1776) was correlated with eight of 14 FA phenotypes. Also, 759 DCO genes were listed, and the oleic acid (n = 358) and monounsaturated fatty acids sum (n = 120) were the most frequent. Furthermore, 243 and 13, 319 and seven, and 173 and 12 gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were enriched respectively for the DEG, COE, and DCO analyses. Combining the results, we highlight the unexplored GIPC2, ASB5, and PPP5C genes in cattle. Besides LIPE and INSIG2 genes in COE modules, the ACSL3, ECI1, DECR2, FITM1, and SDHB genes were signaled in at least two analyses. These findings contribute to understand the genetic mechanisms underlying the beef FA profile in Nellore beef cattle finished in feedlot. [ABSTRACT FROM AUTHOR]

The Manila clam (Ruditapes philippinarum) is one of the most important aquaculture species and widely distributed along the coasts of China, Japan, and Korea. Due to its wide distribution, it can tolerate a wide range of temperature. Studying the gene expression profiles of clam gills had found differentially expressed genes (DEGs) and pathway involved in temperature stress tolerance. A systematic study of cellular response to temperature stress may provide insights into the mechanism of acquired tolerance. Here, weighted gene co-expression network analysis (WGCNA) was carried out using RNA-seq data from gill transcriptome in response to high and low temperature stress. There are a total 32 gene modules, of which 18 gene modules were identified as temperature-related modules. Blue module was one significantly correlated with temperature which was associated with cellular metabolism, apoptosis pathway, ER stress, and others. [ABSTRACT FROM AUTHOR]

Yu-Xin Wang,1,* Feng-Lian Li,1,* Li-Xin Du,1 Jun-Fang Liu,2 Li-Gang Huo,1 Shu-Qing Li,3 Bin Tian1 1Department of Clinical Laboratory, Hengshui Fifth People’s Hospital, Hengshui City, 053000, People’s Republic of China; 2Department of Pathology, Hengshui Fifth People’s Hospital, Hengshui City, 053000, People’s Republic of China; 3Department of cardiothoracic surgery, Hengshui Fifth People’s Hospital, Hengshui City, 053000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng-Lian LiDepartment of Clinical Laboratory, Hengshui Fifth People’s Hospital, No. 1638 Shengli West Road, Hengshui City, Hebei Province, 053000, People’s Republic of ChinaTel +86 318-2316645Email fenglianlidr@163.comObjective: The aim of this study was to quantify the expression of melanoma-antigen family A proteins (MAGE-A) and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) in breast cancer and establish the prognosis of breast cancer patients with MAGE-A and NY-ESO-1 co-expression.Methods: A total of 122 patients with breast cancer were recruited for this study. Their clinicopathological data were collected retrospectively, and the MAGE-A and NY-ESO-1 expressions in paraffin-embedded specimens from the 122 patients were evaluated using immunohistochemical analysis. In addition, the survival states of the patients were recorded.Results: Fifty-four patients (44.26%) were MAGE-A positive and 46 (37.70%) were NY-ESO-1 positive. Interestingly, 22 of the 46 NY-ESO-1-positive cases co-expressed MAGE-A. The expression of MAGE-A was positively associated with estrogen-receptor status (χ2 = 4.026, p = 0.045) and human epidermal growth factor receptor 2 status (χ2 = 5.482, p = 0.019), while the expression of NY-ESO-1 was positively associated with p53 expression (χ2 = 4.541, p = 0.033). Of the 122 patients, the lowest survival rate was observed in patients with NY-ESO-1 (+)/MAGE-A (+), with a 5-year survival rate of 59.09% and a median survival of 97 months.Conclusion: The results showed that MAGE-A and NY-ESO-1 were frequently expressed in breast cancer patients. The co-expression of MAGE-A and NY-ESO-1 occurred in about 18% of these patients, and it may indicate a poor prognosis.Keywords: breast cancer, cancer/testis antigens, MAGE-A, NY-ESO-1, co-expression

Objective To systematically characterize the dynamic expression pattern, stage specificity and co-expression pattern of RNA-binding protein (RBPs) and to predict their potential regulatory role in mouse spermatogenesis. Methods The whole transcriptome sequencing data of six spermatogenic cells types were integrated for analyzing the differentially expressed RBPs during spermatogenesis;STEM was used to analyze the dynamic expression pattern of RBPs; WGCNA was used to identify the RBPs co-expressed pattern; The differentially expressed and co-expressed RBPs were analyzed by the ClusterProfiler tool for GO function enrichment analysis. Results A total of 519 stage-specific RBPs were identified during spermatogenesis, and there were 7 dynamic expression patterns, of which RBPs at the meiotic stage accounted for the highest proportion; GO enrichment analysis showed that RBPs were mainly involved in the selective splicing, processing or translation of mRNA; WGCNA analysis showed that 246 RBPs were co-expressed, among which RBPs at the meiotic stage accounted for the highest proportion. Conclusions RBPs exhibit stage specificity and play a regulatory role in spermatogenesis with a coordinated expression mode. It functions mainly in the process of RNA processing or splicing in the early stage of spermatogenesis, and is have significant impact on the process of ribosome assembly or RNA translation in the later stage.

Abstract Background Low-risk human papillomavirus (HPV), such as types 6 and 11, is considered non-oncogenic, but these types have been detected in oral cancer tissue samples, suggesting their possible involvement in oral carcinogenesis. Because double infection of high-risk HPV and Epstein-Barr virus (EBV) is known to be involved in oral carcinogenesis, we hypothesized that low-risk HPV and EBV co-infection can transform the oral cells. To verify our hypothesis, we evaluated the transformation activity of cell lines expressing both low-risk HPV E6/E7 and EBV LMP-1. Methods We transduced HPV6, 11 and 16 E6/E7 genes and EBV LMP-1 gene into primary mouse embryonic fibroblasts. The cell lines were examined for indices of transformation activity such as proliferation, induction of DNA damage, resistance to apoptosis, anchorage-independent growth, and tumor formation in nude mice. To evaluate the signaling pathways involved in transformation, NF-κB and p53 activities were analyzed. We also assessed adhesion signaling molecules associated with anchorage-independent growth such as MMP-2, paxillin and Cat-1. Results Co-expression of low-risk HPV6 E6 and EBV LMP-1 showed increased cell proliferation, elevated NF-κB activity and reduced p53 induction. Moreover, co-expression of low-risk HPV6 E6 and EBV LMP-1 induced DNA damage, escaped from apoptosis under genotoxic condition and suppression of DNA damage response (DDR). Co-expression of low-risk HPV11 E6/E7 and EBV LMP-1 demonstrated similar results. However, it led to no malignant characteristics such as anchorage-independent growth, invasiveness and tumor formation in nude mice. Compared with the cells co-expressing high-risk HPV16 E6 and EBV LMP-1 that induce transformation, co-expression of low-risk HPV6 E6 and EBV LMP-1 was associated with low MMP-2, paxillin and Cat-1 expression. Conclusions The co-expression of low-risk HPV E6/E7 and EBV LMP-1 does not induce malignant transformation, but it allows accumulation of somatic mutations secondary to increased DNA damage and suppression of DDR. Thus, double infection of low-risk HPV and EBV could lead to precancerous lesions.

Chapter 6, similarly, gives descriptions of analysis pipelines comprising of detailed preprocessing procedures followed by methodologies to conduct differential gene expression (DE) analysis. Keywords: artificial intelligence (AI); co-expression; differential-expression (DE); gene expression; statistical analysis EN artificial intelligence (AI) co-expression differential-expression (DE) gene expression statistical analysis 526 528 3 03/24/23 20230301 NES 230301 Gene expression profiling and analysis is an important research area that helps fathoming the underlying molecular mechanisms of complex diseases. Artificial intelligence (AI), co-expression, differential-expression (DE), gene expression, statistical analysis. [Extracted from the article]

Arabidopsis thaliana contains a family of nine genes known as plant intracellular Ras-group related leucine-rich repeat (LRR) proteins (PIRLs). These are structurally similar to animals and fungal LRR proteins and play important roles in developmental pathways. However, to date, no detailed tissue-specific expression analysis of these PIRLs has been performed. Therefore, in this study, we generated promoter:GUS transgenic plants for the nine A. thaliana PIRL genes and identified their expression patterns in seedlings and floral organs at different developmental stages. Most PIRL members showed expression in the root apical region and in the vascular tissue of primary and lateral roots. Shoot apex-specific expression was recorded for PIRL1 and PIRL8. Furthermore, PIRL1, PIRL3, PIRL5, PIRL6, and PIRL7 showed distinct expression patterns in flowers, especially in pollen and anthers. In addition, co-expression network analysis identified cases where PIRLs were co-expressed with other genes known to have specific functions related to growth and development. Taken together, the tissue-specific expression patterns of PIRL genes improve our understanding of the functions of this gene family in plant growth and development.

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is genetically altered in several cancers, including NSCLC, melanoma, lymphoma, and other tumors. Although ALK is associated with various cancers, the relationship between ALK expression and patient prognosis in different cancers is poorly understood. Here, using multidimensional approaches, we revealed the correlation between ALK expression and the clinical outcomes of patients with LUAD, melanoma, OV, DLBC, AML, and BC. We analyzed ALK transcriptional expression, patient survival rate, genetic alteration, protein network, and gene and microRNA (miRNA) co-expression. Compared to that in normal tissues, higher ALK expression was found in LUAD, melanoma, and OV, which are associated with poor patient survival rates. In contrast, lower transcriptional expression was found to decrease the survival rate of patients with DLBC, AML, and BC. A total of 202 missense mutations, 17 truncating mutations, 7 fusions, and 3 in-frame mutations were identified. Further, 17 genes and 19 miRNAs were found to be exclusively co-expressed and echinoderm microtubule-associated protein-like 4 (EML4) was identified as the most positively correlated gene (log odds ratio >3). The gene ontology and signaling pathways of the genes co-expressed with ALK in these six cancers were also identified. Our findings offer a basis for ALK as a prognostic biomarker and therapeutic target in cancers, which will potentially contribute to precision oncology and assist clinicians in identifying suitable treatment options.

Abstract Background This study aimed to investigate the association between clinicopathologic factors, mesothelin, and cancer antigen (CA) 125 in endometrial carcinoma. Methods Between 1989 and 2017, patients with endometrial carcinoma who underwent total hysterectomy and bilateral salpingo-oophorectomy at our hospital were identified. The association between either or both immunochemical expression of mesothelin and CA125 and clinicopathological features were retrospectively examined. Results Among 485 patients, 171 were positive for mesothelin, 368 were positive for CA125, and 167 were positive for mesothelin and CA125. The expression of mesothelin and CA125 was positively correlated (p

Abstract Background Co-expression correlations provide the ability to predict gene functionality within specific biological contexts, such as different tissue and disease conditions. However, current gene co-expression databases generally do not consider biological context. In addition, these tools often implement a limited range of unsophisticated analysis approaches, diminishing their utility for exploring gene functionality and gene relationships. Furthermore, they typically do not provide the summary visualizations necessary to communicate these results, posing a significant barrier to their utilization by biologists without computational skills. Results We present Correlation AnalyzeR, a user-friendly web interface for exploring co-expression correlations and predicting gene functions, gene–gene relationships, and gene set topology. Correlation AnalyzeR provides flexible access to its database of tissue and disease-specific (cancer vs normal) genome-wide co-expression correlations, and it also implements a suite of sophisticated computational tools for generating functional predictions with user-friendly visualizations. In the usage example provided here, we explore the role of BRCA1-NRF2 interplay in the context of bone cancer, demonstrating how Correlation AnalyzeR can be effectively implemented to generate and support novel hypotheses. Conclusions Correlation AnalyzeR facilitates the exploration of poorly characterized genes and gene relationships to reveal novel biological insights. The database and all analysis methods can be accessed as a web application at https://gccri.bishop-lab.uthscsa.edu/correlation-analyzer/ and as a standalone R package at https://github.com/Bishop-Laboratory/correlationAnalyzeR .

ABL, a human tyrosine protein kinase, and its substrate are co-expressed in Escherichia coli. Tyrosine phosphorylation of the substrate in E. coli was detected using Phos-tag SDS-PAGE. The bacterial co-expression system was used as a field for the kinase reaction to evaluate the enzymatic activity of five types of ABL kinase domain mutants. Relative to wild-type ABL, kinase activity was comparable in the H396P mutant, reduced in both Y253F and E255K mutants and undetectable in T315I and M351T mutants. These comparative results demonstrated that the phosphorylation states of the mutants correlated with their activity. The bacterial co-expression system permits rapid production of tyrosine kinase variants and provides a simple approach for examining their structure–activity relationships.

The MYB transcription factor is one of the largest gene families in plants, playing an important role in regulating plant growth, development, response to stress, senescence, and especially the anthocyanin biosynthesis. In this study, A total of 217 MYB genes, including 90 1R-MYBs, 124 R2R3-MYBs, and 3 R1R2R3-MYBs have been identified from the potato genome. The 1R-MYB and R2R3-MYB family members could be divided into 20 and 35 subgroups respectively. Analysis of gene structure and protein motifs revealed that members within the same subgroup presented similar exon/intron and motif organization, further supporting the results of phylogenetic analysis. Potato is an ideal plant to reveal the tissue-specific anthocyanins biosynthesis regulated by MYB, as the anthocyanins could be accumulated in different tissues, showing colorful phenotypes. Five pairs of colored and colorless tissues, stigma, petal, stem, leaf, and tuber flesh, were applied to the transcriptomic analysis. A total of 70 MYB genes were found to be differentially expressed between colored and colorless tissues, and these differentially expressed genes were suspected to regulate the biosynthesis of anthocyanin of different tissues. Co-expression analysis identified numerous potential interactive regulators of anthocyanins biosynthesis, involving 39 MYBs, 24 bHLHs, 2 WD-repeats, and 29 biosynthesis genes. Genome-wide association study (GWAS) of tuber flesh color revealed a major signal at the end of Chromosome 10, which was co-localized with reported I gene (StMYB88), controlling tuber peel color. Analyses of DEGs (Differentially Expression Genes) revealed that both StMYB88 and StMYB89 were closely related to regulating anthocyanin biosynthesis of tuber flesh. This work offers a comprehensive overview of the MYB family in potato and will lay a foundation for the functional validation of these genes in the tissue-specific regulation of anthocyanin biosynthesis.

Abstract Background Viruses cause significant economic losses to shrimp aquaculture worldwide. In severe cases, they can lead to 100% mortality within a matter of days, hence the aquaculture industry requires antiviral strategies to minimize economic impacts. Currently, a double-stranded RNA (dsRNA)-based platform has been proven effective at a laboratory scale. The bottleneck for its industrialization is the lack of low-cost, efficient and practical delivery approaches. In an effort to bridge the gap between laboratory and farm applications, virus-like particles (VLP) have been used as nanocarriers of dsRNA. However, the implementation of this approach still suffers from high costs and a lengthy procedure, co-expression of subunits of VLP or capsid proteins (CPs) and dsRNA can be the solution for the problem. CP and dsRNA are traditionally expressed in two different E. coli hosts: protease-deficient and RNase III-deficient strains. To condense the manufacturing of dsRNA-containing VLP, this study constructed a novel E. coli strain that is able to co-express viral capsid proteins and dsRNA in the same E. coli cell. Results A novel bacterial strain DualX-B15(DE3) was engineered to be both protease- and RNase III-deficiency via P1 phage transduction. The results revealed that it could simultaneously express recombinant proteins and dsRNA. Conclusion Co-expression of viral capsid proteins and dsRNA in the same cell has been shown to be feasible. Not only could this platform serve as a basis for future cost-effective and streamlined production of shrimp antiviral therapeutics, it may be applicable for other applications that requires co-expression of recombinant proteins and dsRNA.

Single-cell RNA sequencing (scRNA-seq) is an attractive technology for researchers to gain valuable insights into the cellular processes and cell type diversity present in all tissues. The data generated by the scRNA-seq experiment are high-dimensional and complex in nature. Several tools are now available to analyze the raw scRNA-seq data from public databases; however, simple and easy-to-explore single-cell gene expression visualization tools focusing on differential expression and co-expression are lacking. Here, we present scViewer, an interactive graphical user interface (GUI) R/Shiny application designed to facilitate the visualization of scRNA-seq gene expression data. With the processed Seurat RDS object as input, scViewer utilizes several statistical approaches to provide detailed information on the loaded scRNA-seq experiment and generates publication-ready plots. The major functionalities of scViewer include exploring cell-type-specific gene expression, co-expression analysis of two genes, and differential expression analysis with different biological conditions considering both cell-level and subject-level variations using negative binomial mixed modeling. We utilized a publicly available dataset (brain cells from a study of Alzheimer’s disease to demonstrate the utility of our tool. scViewer can be downloaded from GitHub as a Shiny app with local installation. Overall, scViewer is a user-friendly application that will allow researchers to visualize and interpret the scRNA-seq data efficiently for multi-condition comparison by performing gene-level differential expression and co-expression analysis on the fly. Considering the functionalities of this Shiny app, scViewer can be a great resource for collaboration between bioinformaticians and wet lab scientists for faster data visualizations.

Fructose 1,6-bisphosphate aldolase (FBA) is a pivotal enzyme, which plays a critical role in fixing CO 2 through the process of in the Calvin cycle. In this study, a comprehensive exploration of the FBA family genes in moso bamboo (Phyllostachys edulis) was conducted by the bioinformatics and biological analyses. A total of nine FBA genes (PeFBA1 - PeFBA9) were identified in the moso bamboo genome. The expression patterns of PeFBA s across diverse tissues of moso bamboo suggested that they have multifaceted functionality. Notably, PeFBA8 might play an important role in regulating photosynthetic carbon metabolism. Co-expression and cis -element analyses demonstrated that PeFBA8 was regulated by a photosynthetic regulatory transcription factor (PeGLK1), which was confirmed by yeast one-hybrid and dual-luciferase assays. In-planta gene editing analysis revealed that the edited PeFBA8 mutants displayed compromised photosynthetic functionality, characterized by reduced electron transport rate and impaired photosystem I, leading to decreased photosynthesis rate overall, compared to the unedited control. The recombinant protein of PeFBA8 from prokaryotic expression exhibited enzymatic catalytic function. The findings suggest that the expression of PeFBA8 can affect photosynthetic efficiency of moso bamboo leaves, which underlines the potential of leveraging PeFBA8 's regulatory mechanism to breed bamboo varieties with enhanced carbon fixation capability. [ABSTRACT FROM AUTHOR]

Chamaecyparis obtusa and C. obtusa var. formosana of the Cupressaceae family are well known for their fragrance and excellent physical properties. To investigate the biosynthesis of unique diterpenoid compounds, diterpene synthase genes for specialized metabolite synthesis were cloned from C. obtusa and C. obtusa var. formosana. Using an Escherichia coli co-expression system, eight diterpene synthases (diTPSs) were characterized. CoCPS and CovfCPS are class II monofunctional (+)-copalyl diphosphate synthases [(+)-CPSs]. Class I monofunctional CoLS and CovfLS convert (+)-copalyl diphosphate [(+)-CPP] to levopimaradiene, CoBRS, CovfBRS1, and CovfBRS3 convert (+)-CPP to (-)-beyerene, and CovfSDS converts (+)-CPP to (-)-sandaracopimaradiene. These enzymes are all monofunctional diterpene syntheses in Cupressaceae family of gymnosperm, and differ from those in Pinaceae. The discovery of the enzyme responsible for the biosynthesis of tetracyclic diterpene (-)-beyerene was characterized for the first time. Diterpene synthases with different catalytic functions exist in closely related species within the Cupressaceae family, indicating that this group of monofunctional diterpene synthases is particularly prone to the evolution of new functions and development of species-specific specialized diterpenoid constituents. • There are all monofunctional class diTPSs for specialized diterpenoid syntheses in gymnosperm Cupressaceae family. • Specialized tri- and tetracyclic diterpene synthases were found in Chamaecyparis obtusa and C. obtusa var. formosana • The enzyme capable of converting (+)-CPP to beyerene is discovered for the first time in this study. [ABSTRACT FROM AUTHOR]

N-terminal acetyltransferases (NAT) are the protein complexes that deposit the abundant N-terminal acetylation (Nt-Ac) on eukaryotic proteins, with seven human complexes currently identified. Despite the increasing recognition of their biological and clinical importance, NAT regulation remains elusive. In this study, we performed a bioinformatic investigation to identify transcriptional and post-transcriptional processes that could be involved in the regulation of human NAT complexes. First, co-expression analysis of independent transcriptomic datasets revealed divergent pathway associations for human NAT, which are potentially connected to their distinct cellular functions. One interesting connection uncovered was the coordinated regulation of the NatA and proteasomal genes in cancer and immune cells, confirmed by analysis of multiple datasets and in isolated primary T cells. Another distinctive association was of NAA40 (NatD) with DNA replication, in cancer and non-cancer settings. The link between NAA40 transcription and DNA replication is potentially mediated through E2F1, which we have experimentally shown to bind the promoter of this NAT. Second, the coupled examination of transcriptomic and proteomic datasets revealed a much greater intra-complex concordance of NAT subunits at the protein compared to the transcript level, indicating the predominance of post-transcriptional processes for achieving their coordination. In agreement with this concept, we also found that the effects of somatic copy number alterations affecting NAT genes are attenuated post-transcriptionally. In conclusion, this study provides novel insights into the regulation of human NAT complexes. [ABSTRACT FROM AUTHOR]

Targeting protein for Xenopus kinesin-like protein 2 (TPX2), a well-known mitotic protein, has been linked to carcinogenesis in several cancers. This study investigated the role of TPX2 in hepatocellular carcinoma (HCC) from various aspects using bioinformatic analyses. TPX2 expression and its prognostic value in pan-cancers were analyzed using SangerBox. TPX2 expression and its association with prognosis, immune infiltration, tumor mutations, and signaling pathways in HCC were analyzed using UALCAN, BoxKaplan-Meier Plotter, GEPIA, Human Protein Atlas, TIMER 2.0, and SangerBox. Genes co-expressed with TPX2 in HCC were analyzed using the HCCDB database, followed by functional enrichment using SangerBox. Clinical predictive models were established based on TPX2 and its co-expressed genes using the ACLBI database. TPX2 expression significantly increased in pan-cancers and was associated with survival in nearly half of the cancer types. High TPX2 expression has been linked to poor survival outcomes in patients with HCC. TPX2 expression was positively correlated with abundant infiltration of immune cells (including B cells, CD4 + /CD8 + T cells, macrophages, neutrophils, and dendritic cells), TP53 mutation, and carcinogenesis-related pathways, such as the PI3K/AKT/mTOR pathway, cellular response to hypoxia, and tumor proliferation signature. Nineteen genes were found to be co-expressed with TPX2 in HCC, and these genes showed close positive correlations and were mainly implicated in cell cycle-related functions. A prognostic model established using TPX2 and its expressed genes could stratify HCC patients into high- and low-risk groups, with a significantly shorter survival time in high-risk groups. The prognostic model performed well in predicting 1-, 3-, and 5-year survival of patients with HCC, with areas under the curve of 0.801, 0.725, and 0.711, respectively. TPX2 functions as an oncogene in HCC, and its high expression is detrimental to the survival of patients with HCC. Thus, TPX2 may be a prognostic biomarker and potential therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Plant growth is a complex process controlled by a variety of genetic and environmental variables. Nitraria sibirica Pall. is a multi-purpose euhalophyte with economic and medicinal value. However, the molecular mechanisms underlying the changes at different growth stages in N. sibirica remain unreported. In this study, the morphology and physiological characteristics of N. sibirica were compared at the vegetative, full flowering, and fruiting stages. Metabolomics and transcriptomics were used to describe metabolite accumulation and transcriptome expression at different stages, and the relationship between gene expression patterns and metabolite accumulation was studied based on a joint analysis of the two approaches. The results indicated significant variations in the morphological and physiological characteristics of N. sibirica at different growth stages (P < 0.05). Transcriptome and metabolome samples corresponding to the three stages were clearly distinguished, and the metabolite and gene module showed high consistency. The amount of DEMs and DEGs decreased as leaf growth progressed. Differentially expressed genes (DEGs) predominantly belonged to the MYB transcription family, whereas differentially expressed metabolites (DEMs) were dominated by lipids and lipid-like molecules. DEGs were mainly enriched in plant hormone signal transduction, cutin, suberine, and wax biosynthesis pathways, whereas DEMs were mainly enriched in linoleic acid, alpha-linolenic acid metabolism, and phenylpropane biosynthesis pathways. Combined transcriptomic and metabolomic analyses revealed that plant hormone signal transduction, linoleic acid, alpha-linolenic acid, cutin, suberine, and wax biosynthesis were the most significant key pathways for the co-enrichment of DEMs and DEGs. Pearson correlation analysis showed that physiological traits were strongly correlated with DEGs, whereas morphological traits were strongly correlated with DEMs. Moreover, a strong correlation was also observed between DEMs and DEGs. In conclusion, this research provides insights into the metabolic and transcriptional regulatory networks involved in plant development. [Display omitted] • N. sibirica's growth was mediated by plant hormones. • Metabolic module and gene module showed high consistency. • Plant hormone signaling and lipid metabolism were co-enriched. • Physiological processes and metabolite synthesis were regulated by genes. [ABSTRACT FROM AUTHOR]

'Dongzao' (Ziziphus jujuba 'Dongzao') is an economically important fresh fruit well known for its distinctive flavor and significant nutritional benefits. However, dynamic alterations in the genetic and metabolic networks that regulate the development of 'Dongzao' pulp are not fully elucidated. In this study, first, a metabolic regulatory network was constructed. Next, the metabolic landscape of the 'Dongzao' jujube fruit pulp was established during development and ripening by using a joint analysis of metabolomic and transcriptomic data. This dataset was used to establish a global map of changes in the major metabolites throughout 'Dongzao' pulp development. The potential regulatory networks were then dissected, and the key structural genes and transcription factors associated with modulating the metabolism of important jujube fruit ingredients were identified. Further bioinformatics analyses and transient gene overexpression revealed that ZjSHINE3 and ZjNAC29 act as key transcription factors involved in sucrose and malic acid accumulation, respectively. In summary, this study provides novel insights into the metabolic regulatory networks underlying jujube fruit pulp development and generates a useful resource for genetic improvement and breeding studies of jujube. • Metabolomic and transcriptomic analyses of 'Dongzao' pulp were performed. • Metabolic regulatory networks for major 'Dongzao' pulp metabolites were constructed. • Six structural genes and 84 transcription factors, were highly related to sucrose biosynthesis. • Fourteen structural genes and 85 transcription factors, were highly related to malic acid biosynthesis. [ABSTRACT FROM AUTHOR]

Anthracyclines are an important class of natural antitumor drugs. They have a conservative aromatic tetracycline backbone that is substituted with different deoxyglucoses. The deoxyglucoses are crucial for the biological activity of many bacterial natural products after the proper modification from glycosyltransferases (GTs). The difficulty in obtaining highly purified active GTs has prevented biochemical studies on natural product GTs. In this paper, a new Escherichia coli fusion plasmid pGro7′, which introduces the Streptomyces coelicolor chaperone genes groEL1, groES and groEL2, was constructed. The glycosyltransferase DnmS from Streptomyces peucetius ATCC 27952 was co-expressed with the plasmid pGro7′, and unprecedented high-efficiency and soluble expression of DnmS in the E. coli expression system was realized. Subsequently, the reverse glycosylation reaction characteristics of DnmS and DnmQ were verified. We found that DnmS and DnmQ had the highest enzyme activity when they participated in the reaction at the same time. These studies provide a strategy for the soluble expression of GTs in Streptomyces and confirm the reversibility of the catalytic reaction of GTs. This provides a powerful method for the production of active anthracyclines and to enhance the diversity of natural products.

More and more cancer-associated genes (CAGs) are being identified with the development of biological mechanism research. Integrative analysis of protein-protein interaction (PPI) networks and co-expression patterns of these genes can help identify new disease-associated genes and clarify their importance in specific diseases. This study proposed a PPI network and co-expression integration analysis model (PRNet) to integrate PPI networks and gene co-expression patterns to identify potential risk causative genes for pancreatic adenocarcinoma (PAAD). We scored the importance of the candidate genes by constructing a high-confidence co-expression-based edge-weighted PPI network, extracting protein regulatory sub-networks by random walk algorithm, constructing disease-specific networks based on known CAGs, and scoring the genes of the sub-networks with the PageRank algorithm. The results showed that our screened top-ranked genes were more critical in tumours relative to the known CAGs list and significantly differentiated the overall survival of PAAD patients. These results suggest that the PRNet method of ranking cancer-associated genes can identify new disease-associated genes and is more informative than the original CAGs list, which can help investigators to screen potential biomarkers for validation and molecular mechanism exploration. [ABSTRACT FROM AUTHOR]

Background: Beef cuts in different regions of the carcass have different meat quality due to their distinct physiological function. The objective of this study was to characterize the region-specific expression differences using comparative transcriptomics analysis among five representative beef cuts (tenderloin, longissimus lumborum, rump, neck, chuck). Results: We obtained 15,701 expressed genes in 30 muscle samples across five regions from carcass meat. We identified a total of 80 region-specific genes (RSGs), ranging from three (identified in the rump cut) to thirty (identified in the longissimus lumborum cut), and detected 25 transcription factors (TFs) for RSGs. Using a co-expression network analysis, we detected seven region-specific modules, including three positively correlated modules and four negatively correlated modules. We finally obtained 91 candidate genes related to meat quality, and the functional enrichment analyses showed that these genes were mainly involved in muscle fiber structure (e.g., TNNI1, TNNT1), fatty acids (e.g., SCD, LPL), amino acids (ALDH2, IVD, ACADS), ion channel binding (PHPT1, SNTA1, SUMO1, CNBP), protein processing (e.g., CDC37, GAPDH, NRBP1), as well as energy production and conversion (e.g., ATP8, COX8B, NDUFB6). Moreover, four candidate genes (ALDH2, CANX, IVD, PHPT1) were validated using RT-qPCR analyses which further supported our RNA-seq results. Conclusions: Our results provide valuable insights into understanding the transcriptome regulation of meat quality in different beef cuts, and these findings may further help to improve the selection for health-beneficial meat in beef cattle. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease characterized by rapid brain cell degeneration affecting different areas of the brain. Hippocampus is one of the earliest involved brain regions in the disease. Modern technologies based on high-throughput data have identified transcriptional profiling of several neurological diseases, including AD, for a better comprehension of genetic mechanisms of the disease. In this study, we investigated differentially expressed genes (DEGs) from six Gene Expression Omnibus (GEO) datasets of hippocampus of AD patients. The identified DEGs were submitted to Weighted correlation network analysis (WGCNA) and ClueGo to explore genes with a higher degree centrality and to comprehend their biological role. Subsequently, MCODE was used to identify subnetworks of interconnected DEGs. Our study found 40 down-regulated genes and 36 up-regulated genes as consensus DEGs. Analysis of the co-expression network revealed ACOT7, ATP8A2, CDC42, GAD1, GOT1, INA, NCALD, and WWTR1 to be genes with a higher degree centrality. ClueGO revealed the pathways that were mainly enriched, such as clathrin coat assembly, synaptic vesicle endocytosis, and DNA damage response signal transduction by p53 class mediator. In addition, we found a subnetwork of 12 interconnected genes (AMPH, CA10, CALY, NEFL, SNAP25, SNAP91, SNCB, STMN2, SV2B, SYN2, SYT1, and SYT13). Only CA10 and CALY are targets of known drugs while the others could be potential novel drug targets. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those originating in the hypopharynx have the worst prognosis. The histone demethylase LSD1 has been shown to promote cancer initiation, progression, and relapse through various mechanisms and is upregulated in many cancer tissues. LSD1 physically interacts with SNAIL and is required for SNAIL mediated transcriptional repression. Previous studies of the prognostic value of LSD1 in HNSCC have been limited in their analysis of sub-sites, and a correlation between LSD1 and SNAIL has not been shown in HNSCC patient samples. Here we used a large, representative, and clinically well-characterized cohort of 339 HNSCC patients to investigate the co-expression of LSD1 and SNAIL and their prognostic value in all HNSCC using immunohistochemical staining. Elevated LSD1 expression correlated with advanced tumor stage and poor progression-free survival (PFS) in HNSCC originating in the hypopharynx. Overexpression of the transcription factor SNAIL independently correlated with worse overall survival (OS) and PFS in HNSCC in general and prominently in tumors of the hypopharynx. Furthermore, increased LSD1 expression significantly correlated with elevated SNAIL expression in patient samples. Therefore, the presented data implicates LSD1 and SNAIL as independent prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Deep RNA sequencing of 164 blood samples collected from long-lived families was performed to investigate the expression patterns of circular RNAs (circRNAs). Unlike that observed in previous studies, circRNA expression in long-lived elderly individuals (98.3 ± 3.4 year) did not exhibit an age-accumulating pattern. Based on weighted circRNA co-expression network analysis, we found that longevous elders specifically gained eight but lost seven conserved circRNA-circRNA co-expression modules (c-CCMs) compared with normal elder controls (spouses of offspring of long-lived individuals, age = 59.3 ± 5.8 year). Further analysis showed that these modules were associated with healthy aging-related pathways. These results together suggest an important role of circRNAs in regulating human lifespan extension. [ABSTRACT FROM AUTHOR]

SUMMARY: Camelina (Camelina sativa) is an annual oilseed plant that is gaining momentum as a biofuel cover crop. Understanding gene regulatory networks is essential to deciphering plant metabolic pathways, including lipid metabolism. Here, we take advantage of a growing collection of gene expression datasets to predict transcription factors (TFs) associated with the control of Camelina lipid metabolism. We identified approximately 350 TFs highly co‐expressed with lipid‐related genes (LRGs). These TFs are highly represented in the MYB, AP2/ERF, bZIP, and bHLH families, including a significant number of homologs of well‐known Arabidopsis lipid and seed developmental regulators. After prioritizing the top 22 TFs for further validation, we identified DNA‐binding sites and predicted target genes for 16 out of the 22 TFs tested using DNA affinity purification followed by sequencing (DAP‐seq). Enrichment analyses of targets supported the co‐expression prediction for most TF candidates, and the comparison to Arabidopsis revealed some common themes, but also aspects unique to Camelina. Within the top potential lipid regulators, we identified CsaMYB1, CsaABI3AVP1‐2, CsaHB1, CsaNAC2, CsaMYB3, and CsaNAC1 as likely involved in the control of seed fatty acid elongation and CsaABI3AVP1‐2 and CsabZIP1 as potential regulators of the synthesis and degradation of triacylglycerols (TAGs), respectively. Altogether, the integration of co‐expression data and DNA‐binding assays permitted us to generate a high‐confidence and short list of Camelina TFs involved in the control of lipid metabolism during seed development. [ABSTRACT FROM AUTHOR]

Background: Soluble cello-oligosaccharides (COS, β‐1,4‐D‐gluco‐oligosaccharides with degree of polymerization DP 2–6) have been receiving increased attention in different industrial sectors, from food and feed to cosmetics. Development of large-scale COS applications requires cost-effective technologies for their production. Cascade biocatalysis by the three enzymes sucrose-, cellobiose- and cellodextrin phosphorylase is promising because it enables bottom-up synthesis of COS from expedient substrates such as sucrose and glucose. A whole-cell-derived catalyst that incorporates the required enzyme activities from suitable co-expression would represent an important step towards making the cascade reaction fit for production. Multi-enzyme co-expression to reach distinct activity ratios is challenging in general, but it requires special emphasis for the synthesis of COS. Only a finely tuned balance between formation and elongation of the oligosaccharide precursor cellobiose results in the desired COS. Results: Here, we show the integration of cellodextrin phosphorylase into a cellobiose-producing whole-cell catalyst. We arranged the co-expression cassettes such that their expression levels were upregulated. The most effective strategy involved a custom vector design that placed the coding sequences for cellobiose phosphorylase (CbP), cellodextrin phosphorylase (CdP) and sucrose phosphorylase (ScP) in a tricistron in the given order. The expression of the tricistron was controlled by the strong T7lacO promoter and strong ribosome binding sites (RBS) for each open reading frame. The resulting whole-cell catalyst achieved a recombinant protein yield of 46% of total intracellular protein in an optimal ScP:CbP:CdP activity ratio of 10:2.9:0.6, yielding an overall activity of 315 U/g dry cell mass. We demonstrated that bioconversion catalyzed by a semi-permeabilized whole-cell catalyst achieved an industrial relevant COS product titer of 125 g/L and a space–time yield of 20 g/L/h. With CbP as the cellobiose providing enzyme, flux into higher oligosaccharides (DP ≥ 6) was prevented and no insoluble products were formed after 6 h of conversion. Conclusions: A whole-cell catalyst for COS biosynthesis was developed. The coordinated co-expression of the three biosynthesis enzymes balanced the activities of the individual enzymes such that COS production was maximized. With the flux control set to minimize the share of insolubles in the product, the whole-cell synthesis shows a performance with respect to yield, productivity, product concentration and quality that is promising for industrial production. [ABSTRACT FROM AUTHOR]

Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin‐5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM− cohorts. The expression pattern of laminin‐5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan–Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin‐5γ2 (p <.001) and MMP2 (p <.001). This pattern was mirrored by the significant upregulation of laminin‐5γ2 and MMP2 in VM+ cohorts compared with the VM− ones. Furthermore, co‐expression of VM and laminin‐5γ2 was significantly associated with tumour grade (p =.010), primary tumour size (p <.001), lymph node metastasis (p =.001) and TNM stages (p <.001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin‐5γ2 double‐positive cohort displayed a significantly poorer disease‐free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin‐5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, p =.028] and OS [HR = 21.401, p =.033] in OSCC patients. Together, our findings imply that VM along with laminin‐5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin‐5γ2 coordination emerges as a critical prognostic biomarker for OSCC. [ABSTRACT FROM AUTHOR]

Phenotypic characterization of γδ T cells in the MALs (malignant ascites lymphocytes), TILs (tumor infiltrating lymphocytes), and PBLs (peripheral blood lymphocytes) of ovarian cancer (OvCA) patients is lacking. Therefore, we quantified γδ T cell prevalence in MAL, TIL, and PBL specimens from n = 18 OvCA patients and PBL from age-matched healthy donors (HD, n = 14). Multicolor flow cytometry was performed to evaluate the expression of inhibitory receptors (TIGIT, PD-1 and TIM-3), stimulatory receptors (Ox40), and purinergic ectoenzymes (CD39 and CD73) on γδ T cell subsets. We identified an abundant infiltration of Vδ1 T cells in the MALs and TILs. These cells varied in their differentiation: The majority of Vδ1 TILs displayed an effector memory (EM) phenotype, whereas Vδ1 MALs had a more mature phenotype of terminally differentiated effector memory cells (TEMRA) with high CD45RA expression. TIGIT and TIM-3 were abundantly expressed in both MALs and PBLs, whereas Vδ1 TILs exhibited the highest levels of PD-1, CD39, and Ox40. We also observed specific clusters on mature differentiation stages for the analyzed molecules. Regarding co-expression, Vδ1 TILs showed the highest levels of cells co-expressing TIGIT with PD-1 or CD39 compared to MALs and PBLs. In conclusion, the Vδ1 T cell population showed a high prevalence in the MALs and primary tumors of OvCA patients. Due to their (co-)expression of targetable immune receptors, in particular TIGIT with PD-1 and CD39 in TILs, Vδ1 T cell-based approaches combined with the inhibition of these targets might represent a promising strategy for OvCA. [ABSTRACT FROM AUTHOR]

Background: Bougainvillea is a popular ornamental plant with brilliant color and long flowering periods. It is widely distributed in the tropics and subtropics. The primary ornamental part of the plant is its colorful and unusual bracts, rich in the stable pigment betalain. The developmental mechanism of the bracts is not clear, and the pathway of betalain biosynthesis is well characterized in Bougainvillea. Results: At the whole-genome level, we found 23,469 protein-coding genes by assembling the RNA-Seq and Iso-Seq data of floral and leaf tissues. Genome evolution analysis revealed that Bougainvillea is related to spinach; the two diverged approximately 52.7 million years ago (MYA). Transcriptome analysis of floral organs revealed that flower development of Bougainvillea was regulated by the ABCE flower development genes; A-class, B-class, and E-class genes exhibited high expression levels in bracts. Eight key genes of the betalain biosynthetic pathway were identified by homologous alignment, all of which were upregulated concurrently with bract development and betalain accumulation during the bract initiation stage of development. We found 47 genes specifically expressed in stamens, including seven highly expressed genes belonging to the pentose and glucuronate interconversion pathways. BgSEP2b, BgSWEET11, and BgRD22 are hub genes and interacted with many transcription factors and genes in the carpel co-expression network. Conclusions: We assembled protein-coding genes of Bougainvilea, identified the floral development genes, and constructed the gene co-expression network of petal, stamens, and carpel. Our results provide fundamental information about the mechanism of flower development and pigment accumulation in Bougainvillea, and will facilitate breeding of cultivars with high ornamental value. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is categorized by rapid malignant cellular growth in the central nervous system (CNS) tumors. It is one of the most prevailing primary brain tumors, particularly in human male adults. Even though the combination therapy comprises surgery, chemotherapy, and adjuvant therapies, the survival rate is on average 14.6 months. Glioma stem cells (GSCs) have key roles in tumorigenesis, progression, and counteracting chemotherapy and radiotherapy. In our study, firstly, the gene expression dataset GSE45117 was retrieved and differentially expressed genes (DEGs) were spotted. The co-expression network analysis was employed on DEGs to find the significant modules. The most significant module resulting from co-expression analysis was the turquoise module. The turquoise module related to the tumor cells, hypoxia, normoxic treatments of glioblastoma tumor (GBT), and GSCs were screened. Sixty-one common genes in the turquoise module were selected generated through the co-expression analysis and protein–protein interaction (PPI) network. Moreover, the GO and KEGG pathway enrichment results were studied. Twenty common hub genes were screened by the NetworkAnalyst web instrument constructed on the PPI network through the STRING database. After survival analysis via the Kaplan–Meier (KM) plotter from The Cancer Genome Atlas (TCGA) database, we identified the five most significant hub genes strongly related to the progression of GBM. We further observed these five most significant hub genes also up-regulated in another GBM gene expression dataset. The protein–protein interaction (PPI) network of the turquoise module genes was constructed and a KEGG pathway enrichments study of the turquoise module genes was performed. The VEGF signaling pathway was emphasized because of the strong link with GBM. A gene–disease association network was further constructed to demonstrate the information of the progression of GBM and other related brain neoplasms. All hub genes assessed through this study would be potential markers for the prognosis and diagnosis of GBM. [ABSTRACT FROM AUTHOR]

Sesame is considered one of India's important sources of edible oil and an excellent dietary source for its nutritional and medicinal value. Sesame DGAT1 and PDAT1 genes were co-expressed with omega 3 FAD genes. Systemic isolation of sesame DGAT1, PDAT1, ER type FAD3, and chloroplast type FAD7/8 genes were performed. Their sequence was analyzed for genomic organization, amino acid characterization, organ specificity, and phylogenetic relationships. The insilico analysis revealed the unique features of DGAT1, PDAT1, and FAD3 gene sequences, whereas FAD7 and FAD8 sequences had the same protein characters and were grouped in phylogeny analysis, only variation was found in their mRNA UTR regions. Functional expression of sesame TAG synthesis genes and omega-3 FAD genes was studied in yeast mutant H1246 deficient for TAG synthesis. Functional analyses in yeast with the presence of ALA confirmed the identity of sesame FAD3, FAD7 and FAD8 genes. Recombinant expression of pESC + DGAT1 + FAD3 vector in yeast mutant resulted in lipid accumulation with 10% higher ALA content. Thus this gene combination can be co-expressed in sesame and other plant systems to increase the lipid accumulation with high omega-3 fatty acid (ALA) content. [ABSTRACT FROM AUTHOR]