The loss of ITGA2 plays an important role in cancer metastasis in several solid cancers. However, the molecular mechanism of ITGA2 loss in primary cancers remains unclear. In this study, we found ...that a lower ITGA2 protein level was observed in breast cancers compared to adjacent non-cancerous breast tissues. Interestingly, the reduction degree of ITGA2 at the protein level was far more than that at the mRNA level. We further showed that the translation of ITGA2 mRNA was directly inhibited by miR-373 through binding to ITGA2-3'UTR. Silencing of ITGA2 detached cell-cell interactions, induced the deploymerization of stress fiber F-actin and stimulated cancer cell migration, similar to the effect of miR-373 over-expression. The co-expression of ITGA2, not ITGA2-3'UTR, could abrogate miR-373-induced cancer cell migration because that the expression of ITGA2-3'UTR was inhibited by co-transfected miR-373. ITGA2 protein level was inversely associated with miR-373 level in breast cancers (r = -0.663, P<0.001). 73.33% of breast cancer patients with high miR-373 and low ITGA2 expression exhibited the lymph node-positive metastases. Together, our results show that epigenetic silencing of ITGA2 by miR-373 stimulates breast cancer migration, and miR-373high/ITGA2low may be as a prognosis biomarker for breast cancer patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cultivated peanut (Arachis hypogaea), a progeny of the cross between A. duranensis and A. ipaensis, is an important oil and protein crop from South America. To date, at least six Arachis genomes have ...been sequenced. WRKY transcription factors (TFs) play crucial roles in plant growth, development, and response to abiotic and biotic stresses. WRKY TFs have been identified in A. duranensis, A. ipaensis, and A. hypogaea cv. Tifrunner; however, variations in their number and evolutionary patterns across various Arachis spp. remain unclear.
WRKY TFs were identified and compared across different Arachis species, including A. duranensis, A. ipaensis, A. monticola, A. hypogaea cultivars (cv.) Fuhuasheng, A. hypogaea cv. Shitouqi, and A. hypogaea cv. Tifrunner. The results showed that the WRKY TFs underwent dynamic equilibrium between diploid and tetraploid peanut species, characterized by the loss of old WRKY TFs and retention of the new ones. Notably, cultivated peanuts inherited more conserved WRKY orthologs from wild tetraploid peanuts than their wild diploid donors. Analysis of the W-box elements and protein-protein interactions revealed that different domestication processes affected WRKY evolution across cultivated peanut varieties. WRKY TFs of A. hypogaea cv. Fuhuasheng and Shitouqi exhibited a similar domestication process, while those of cv. Tifrunner of the same species underwent a different domestication process based on protein-protein interaction analysis.
This study provides new insights into the evolution of WRKY TFs in Arachis spp.
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It has been reported that about 30% of the HLA-I ligands are produced by proteasomal splicing of two noncontiguous fragments of a parental protein. We report that the identification of many of those ...spliced peptides is ambiguous. With an alternative workflow, based on de novo sequencing and subsequent verification with multiple search tools, we estimate that the upper bound for the proportion of cis-spliced peptides is 2–6%. Nevertheless, the true contribution of spliced peptides to the ligandome may be much smaller.
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Highlights
•Reported proteasomal spliced HLA peptides do not fit the consensus binding motifs.•Their MS/MS spectrum matches suggest that many of them are ambiguous.•Our workflow is based on de novo sequencing, alignment, and multiple search tools.•The upper bound proportion of cis-spliced peptides is 2–6% and likely much smaller.
Spliced peptides are short protein fragments spliced together in the proteasome by peptide bond formation. True estimation of the contribution of proteasome-spliced peptides (PSPs) to the global human leukocyte antigen (HLA) ligandome is critical. A recent study suggested that PSPs contribute up to 30% of the HLA ligandome. We performed a thorough reanalysis of the reported results using multiple computational tools and various validation steps and concluded that only a fraction of the proposed PSPs passes the quality filters. To better estimate the actual number of PSPs, we present an alternative workflow. We performed de novo sequencing of the HLA-peptide spectra and discarded all de novo sequences found in the UniProt database. We checked whether the remaining de novo sequences could match spliced peptides from human proteins. The spliced sequences were appended to the UniProt fasta file, which was searched by two search tools at a false discovery rate (FDR) of 1%. We find that 2–6% of the HLA ligandome could be explained as spliced protein fragments. The majority of these potential PSPs have good peptide-spectrum match properties and are predicted to bind the respective HLA molecules. However, it remains to be shown how many of these potential PSPs actually originate from proteasomal splicing events.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Large-scale group decision-making (LSGDM) is a complex process involving numerous decision-makers (DMs). However, considering such a large number of DMs increases the complexity of the process. it ...seems necessary to pay much more attention to aspects such as a proper dimensionality reduction for scalability, consensus processes with automatic feedback, and effective management of non-cooperative DMs. To address such aspects, this paper presents a novel framework for LSGDM, based on Extended Comparative Linguistic Expressions With Symbolic Translation (ELICIT). We first extend the K-means clustering algorithm by incorporating individual assessments and trust relationships to classify DMs into subgroups, enhancing decision-making efficiency. We then develop a feedback mechanism based on two optimization consensus models for ELICIT information, that automatically provides optimal recommendations. An essential aspect of our proposal is the management of non-cooperative behaviors by utilizing the normal distribution to detect and penalize misbehaviors. Furthermore, we introduce a Data Envelopment Analysis (DEA) cross-efficiency method based on ELICIT values to rank all alternatives once an acceptable group consensus degree is reached. The framework’s effectiveness is demonstrated through a practical application case study, accompanied by a parametric analysis. Comparisons with existing LSGDM methods highlight the superiority of our proposal in terms of efficiency.
•A K-Means clustering algorithm based on ELICIT information and trust relationships is generalized.•A novel feedback mechanism based on two optimization models is built.•A novel approach for identifying and managing non-cooperative behavior is constructed.•An extended DEA cross-efficiency model for ranking alternatives is employed.•A novel large-scale group decision-making framework is developed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The role of Fat Mass and Obesity-associated protein （FTO） and its substrate N6-methyladenosine （m6A） in mRNA processing and adipogenesis remains largely unknown. We show that FTO expression and m6A ...levels are inversely correlated during adipogenesis. FTO depletion blocks differentiation and only catalytically active FTO restores adi- pogenesis. Transcriptome analyses in combination with m6A-seq revealed that gene expression and mRNA splicing of grouped genes are regulated by FTO. M6A is enriched in exonic regions flanking 5＇- and 3＇-splice sites, spatially over- lapping with mRNA splicing regulatory serine/arginine-rich （SR） protein exonic splicing enhancer binding regions. Enhanced levels of m6A in response to FTO depletion promotes the RNA binding ability of SRSF2 protein, leading to increased inclusion of target exons. FTO controls exonic splicing of adipogenie regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation. These findings provide compelling evidence that FTO-dependent m6A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Heavy metal contamination has become a worldwide problem through disturbing the normal functions of rivers and lakes. Sediment, as the largest storage and resources of heavy metal, plays a rather ...important role in metal transformations. This paper provides a review on the geochemical forms, affecting factors and remediation technologies of heavy metal in sediment. The in situ remediation of sediment aims at increasing the stabilization of some metals such as the mobile and the exchangeable fractions; whereas, the ex situ remediation mainly aims at removing those potentially mobile metals, such as the Mn-oxides and the organic matter (OM) fraction. The pH and OM can directly change metals distribution in sediment; however oxidation–reduction potential (ORP), mainly through changing the pH values, indirectly alters metals distribution. Mainly ascribed to their simple operation mode, low costs and fast remediation effects, in situ remediation technologies, especially being fit for slight pollution sediment, are applied widely. However, for avoiding metal secondary pollution from sediment release, ex situ remediation should be the hot point in future research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Calcium deficiency usually causes accelerated quality deterioration in postharvest fruit, whereas the underlining mechanism is still unclear. Here, we report that calcium deficiency induced the ...development of bitter pit on the surface of apple peels compared with the healthy appearance in control apples during postharvest storage. Physiological analysis indicates that calcium-deficient peels contained higher levels of superoxide anion (O2•−), malondialdehyde (MDA), total phenol, flavonoid contents and polyphenol oxidase (PPO) activity, and reduced calcium, H2S production, anthocyanin, soluble protein content, and peroxidase (POD) activity compared with those in calcium-sufficient peels. The principal component analysis (PCA) results show that calcium content, ROS, and H2S production were the main factors between calcium-deficient and calcium-sufficient apple peels. Transcriptome data indicated that four calmodulin-like proteins (CMLs), seven AP2/ERFs, and three bHLHs transcripts were significantly differentially expressed in calcium-deficient apple peels. RT-qPCR and correlation analyses further revealed that CML5 expression was significantly positively correlated with the expression of ERF2/17, bHLH2, and H2S production related genes. In addition, transcriptional co-activation of CML5 by ERF2 and bHLH2 was demonstrated by apple transient expression assays and dual-luciferase reporter system experiments. Therefore, these findings provide a basis for studying the molecular mechanism of postharvest quality decline in calcium-deficient apples and the potential interaction between Ca2+ and endogenous H2S.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Whole tumor cell lysates (TCL) have been implemented as tumor antigens for cancer vaccine development, although clinical outcomes of TCL-based antitumor immunotherapy remain unsatisfactory. ...In order to improve the efficacy of TCL-based vaccines, biomaterials have been employed to enhance antigen delivery and presentation. Here, we have developed chitosan nanoparticles (CTS NPs) with surface mannose (Man) moieties for specific dendritic cells (DCs) targeting (Man-CTS NPs). The Man-CTS NPs were then loaded with TCL generated from B16 melanoma cells (Man-CTS-TCL NPs) for in vitro and in vivo assessment. Potency of the Man-CTS-TCL NPs as cancer vaccine was also assessed in vivo by immunization of mice with Man-CTS-TCL NPs followed by re-challenge with B16 melanoma cell inoculation. We have shown here that Man-CTS-TCL NPs promote bone marrow-derived dendritic cells (BMDCs) maturation and antigen presentation in vitro. In vivo evaluation further demonstrated that the Man-CTS-TCL NPs were readily taken up by endogenous DCs within the draining lymph node (DLN) following subcutaneous administration accompanied by increase in serum IFN-γ and IL-4 levels. Tumor growth was also significantly delayed in mice primed with Man-CTS-TCL NPs vaccine, attributable at least in part to cytotoxic T lymphocytes response. Moreover, Man-CTS-TCL NPs vaccine also exhibited therapeutic effects in mice with melanoma. Thus, we report here the Man-CTS-TCL NPs as effective anti-tumor vaccine for cancer immunotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Many recent studies have shown that miRNAs play important roles in the regulation of animal reproduction, including seasonal reproduction. The pineal gland is a crucial hub in the regulation of ...seasonal reproduction. However, little is known about the expression characteristics of pineal miRNAs in different reproductive seasons (anestrus and breeding season). Therefore, the expression profiles and regulatory roles of ovine pineal miRNAs were investigated during different reproductive stages using Solexa sequencing technology and dual luciferase reporter assays.
A total of 427 miRNAs were identified in the sheep pineal gland. Significant differences in miRNA expression were demonstrated between anestrus and the breeding season in terms of the frequency distributions of miRNA lengths, number of expressed miRNAs, and specifically and highly expressed miRNAs in each reproductive stage. KEGG analysis of the differentially expressed (DE) miRNAs between anestrus and the breeding season indicated that they are significantly enriched in pathways related to protein synthesis, secretion and uptake. Furthermore, transcriptome analysis revealed that many target genes of DE miRNAs in the ribosome pathway showed relatively low expression in the breeding season. On the other hand, analyses combining miRNA-gene expression data with target relationship validation in vitro implied that miR-89 may participate in the negative regulation of aralkylamine N-acetyltransferase (AANAT) mRNA expression by targeting its 3'UTR at a unique binding site.
Our results provide new insights into the expression characteristics of sheep pineal miRNAs at different reproductive stages and into the negative regulatory effects of pineal miRNAs on AANAT mRNA expression.
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