A genome-wide association study reveals a substantial genetic basis underlying the Ebbinghaus illusion.

The Ebbinghaus illusion (EI) is an optical illusion of relative size perception that reflects the contextual integration ability in the visual modality. The current study investigated the genetic basis of two subtypes of EI, EI overestimation, and EI underestimation in humans, using quantitative genomic analyses. A total of 2825 Chinese adults were tested on their magnitudes of EI overestimation and underestimation using the method of adjustment, a standard psychophysical protocol. Heritability estimation based on common single nucleotide polymorphisms (SNPs) revealed a moderate heritability (34.3%) of EI overestimation but a nonsignificant heritability of EI underestimation. A meta-analysis of two phases (phase 1: n = 1986, phase 2: n = 839) of genome-wide association study (GWAS) discovered 1969 and 58 SNPs reaching genome-wide significance for EI overestimation and EI underestimation, respectively. Among these SNPs, 55 linkage-disequilibrium-independent SNPs were associated with EI overestimation in phase 1 with genome-wide significance and their associations could be confirmed in phase 2 cohort. Gene-based analyses found seven genes to be associated with EI overestimation at the genome-wide level, two from meta-analysis, and five from classical two-stage analysis. Overall, this study provided consistent evidence for a substantial genetic basis of the Ebbinghaus illusion.

Genomic Analyses of Visual Cognition: Perceptual Rivalry and Top-Down Control.

Visual cognition in humans has traditionally been studied with cognitive behavioral methods and brain imaging, but much less with genetic methods. Perceptual rivalry, an important phenomenon in visual cognition, is the spontaneous perceptual alternation that occurs between two distinct interpretations of a physically constant visual stimulus (e.g., binocular rivalry stimuli) or a perceptually ambiguous stimulus (e.g., the Necker cube). The switching rate varies dramatically across individuals and can be voluntarily modulated by observers. Here, we adopted a genomic approach to systematically investigate the genetics underlying binocular rivalry, Necker cube rivalry and voluntary modulation of Necker cube rivalry in young Chinese adults (Homo sapiens, 81% female, 20 ± 1 years old) at multiple levels, including common single nucleotide polymorphism (SNP)-based heritability estimation, SNP-based genome-wide association study (GWAS), gene-based analysis, and pathway analysis. We performed a pilot GWAS in 2441 individuals and replicated it in an independent cohort of 943 individuals. Common SNP-based heritability was estimated to be 25% for spontaneous perceptual rivalry. SNPs rs184765639 and rs75595941 were associated with voluntary modulation, and imaging data suggested genotypic difference of rs184765639 in the surface area of the left caudal-middle frontal cortex. Additionally, converging evidence from multilevel analyses associated genes such as PRMT1 with perceptual switching rate, and MIR1178 with voluntary modulation strength. In summary, this study discovered specific genetic contributions to perceptual rivalry and its voluntary modulation in human beings. These findings may promote our understanding of psychiatric disorders, as perceptual rivalry is a potential psychiatric biomarker.SIGNIFICANCE STATEMENT Perceptual rivalry is an important visual phenomenon in which our perception of a physically constant visual input spontaneously switches between two different states. There are individual variations in perceptual switching rate and voluntary modulation strength. Our genomic analyses reveal several loci associated with these two kinds of variation. Because perceptual rivalry is thought to be relevant to and potentially an endophenotype for psychiatric disorders, these results may help understand not only visual cognition, but also psychiatric disorders.

PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth.

PPP3CB belongs to the phosphoprotein phosphatases (PPPs) group. Although the majority of the PPP family play important roles in the epithelial-to-mesenchymal transition (EMT) of tumor cells, little is known about the function of PPP3CB in the EMT process. Here, we found PPP3CB had high expression in kidney mesenchymal-like cells compared with kidney epithelial-like cells. Knock-down of PPP3CB downregulated epithelial marker E-cadherin and upregulated mesenchymal marker Vimentin, promoting the transition of cell states from epithelial to mesenchymal and reorganizing the actin cytoskeleton which contributed to cell migration. Conversely, overexpression of PPP3CB reversed EMT and inhibited migration of tumor cells. Besides, in vitro and in vivo experiments indicated that the loss of PPP3CB suppressed the tumor growth. However, the deletion of the phosphatase domain of PPP3CB showed no effect on the expression of E-cadherin, migration, and G401 cell proliferation. Together, we demonstrate that PPP3CB inhibits G401 cell migration through regulating EMT and promotes cell proliferation, which are both associated with the phosphatase activity of PPP3CB.

Gulo regulates the proliferation, apoptosis and mesenchymal-to-epithelial transformation of metanephric mesenchyme cells via inhibiting Six2.

During kidney development, the balance between self-renewal and differentiation of metanephric mesenchyme (MM) cells, mainly regulated by Sine oculis-related homeobox 2 (Six2), is critical for forming mature kidney. L-gulono-γ-lactone oxidase (Gulo), a crucial enzyme for vitamin C synthesis, reveals a different expression at various stages during kidney development, but its function in the early renal development remains unknown. In this work, we aim to study the role of Gulo in MM cells at two differentiation stages. We found that Gulo expression in undifferentiated MM (mK3) cells was lower than in differentiated MM (mK4) cells. Over-expression of Gulo can promote mesenchymal-to-epithelial transformation (MET) and apoptosis and inhibit the proliferation in mK3 cells. Knock-down of Gulo in mK4 cells made its epithelial character cells unstabilized, facilitated the proliferation and restrained the apoptosis. Furthermore, we found that Six2 was negatively regulated by Gulo, and over-expression or knock-down of Six2 was able to rescue partially the MET, proliferation and apoptosis of MM cells caused by Gulo. In conclusion, these findings reveal that Gulo promotes the MET and apoptosis, and inhibits proliferation in MM cells by down-regulating Six2.

Nature vs. nurture in human sociality: multi-level genomic analyses of social conformity.

Social conformity is fundamental to human societies and has been studied for more than six decades, but our understanding of its mechanisms remains limited. Individual differences in conformity have been attributed to social and cultural environmental influences, but not to genes. Here we demonstrate a genetic contribution to conformity after analyzing 1,140 twins and single-nucleotide polymorphism (SNP)-based studies of 2,130 young adults. A two-step genome-wide association study (GWAS) revealed replicable associations in 9 genomic loci, and a meta-analysis of three GWAS with a sample size of ~2,600 further confirmed one locus, corresponding to the NAV3 (Neuron Navigator 3) gene which encodes a protein important for axon outgrowth and guidance. Further multi-level (haplotype, gene, pathway) GWAS strongly associated genes including NAV3, PTPRD (protein tyrosine phosphatase receptor type D), ARL10 (ADP ribosylation factor-like GTPase 10), and CTNND2 (catenin delta 2), with conformity. Magnetic resonance imaging of 64 subjects shows correlation of activation or structural features of brain regions with the SNPs of these genes, supporting their functional significance. Our results suggest potential moderate genetic influence on conformity, implicate several specific genetic elements in conformity and will facilitate further research on cellular and molecular mechanisms underlying human conformity.

EIYMNVPV Motif is Essential for A1CF Nucleus Localization and A1CF (-8aa) Promotes Proliferation of MDA-MB-231 Cells via Up-Regulation of IL-6.

Apobec-1 complementation factor (A1CF) is a heterogeneous nuclear ribonuceloprotein (hnRNP) and mediates apolipoprotein-B mRNA editing. A1CF can promote the regeneration of the liver by post-transcriptionally stabilizing Interleukin-6 (IL-6) mRNA. It also contains two transcriptional variants-A1CF64 and A1CF65, distinguished by the appearance of a 24-nucleotide motif which contributes to the corresponding eight-amino acid motif of EIYMNVPV. For the first time, we demonstrated that the EIYMNVPV motif was essential for A1CF nucleus localization, A1CF deficient of the EIYMNVPV motif, A1CF (-8aa) showed cytoplasm distribution. More importantly, we found that A1CF (-8aa), but not its full-length counterpart, can promote proliferation of MDA-MB-231 cells accompanied with increased level of IL-6 mRNA. Furthermore, silencing of IL-6 attenuated A1CF (-8aa)-induced proliferation in MDA-MB-231 cells. In conclusion, notably, these findings suggest that A1CF (-8aa) promoted proliferation of MDA-MB-231 cells in vitro viewing IL-6 as a target. Thus, the EIYMNVPV motif could be developed as a potential target for basal-like breast cancer therapy.

Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells.

Nephron progenitor cells surround around the ureteric bud tips (UB) and inductively interact with the UB to originate nephrons, the basic units of renal function. This process is determined by the internal balance between self-renewal and consumption of the nephron progenitor cells, which is depending on the complicated regulation networks. It has been reported that Zeb1 regulates the proliferation of mesenchymal cells in mouse embryos. However, the role of Zeb1 in nephrons generation is not clear, especially in metanephric mesenchyme (MM). Here, we detected cell proliferation, apoptosis and migration in MM cells by EdU assay, flow cytometry assay and wound healing assay, respectively. Meanwhile, Western and RT-PCR were used to measure the expression level of Zeb1 and Six2 in MM cells and developing kidney. Besides, the dual-luciferase assay was conducted to study the molecular relationship between Zeb1 and Six2. We found that knock-down of Zeb1 decreased cell proliferation, migration and promoted cell apoptosis in MM cells and Zeb1 overexpression leaded to the opposite data. Western-blot and RT-PCR results showed that knock-down of Zeb1 decreased the expression of Six2 in MM cells and Zeb1 overexpression contributed to the opposite results. Similarly, Zeb1 promoted Six2 promoter reporter activity in luciferase assays. However, double knock-down of Zeb1 and Six2 did not enhance the apoptosis of MM cells compared with control cells. Nevertheless, double silence of Zeb1 and Six2 repressed cell proliferation. In addition, we also found that Zeb1 and Six2 had an identical pattern in distinct developing phases of embryonic kidney. These results indicated that there may exist a complicated regulation network between Six2 and Zeb1. Together, we demonstrate Zeb1 promotes proliferation and apoptosis and inhibits the migration of MM cells, in association with Six2.

Six2 Is a Coordinator of LiCl-Induced Cell Proliferation and Apoptosis.

The metanephric mesenchyme (MM) cells are a subset of kidney progenitor cells and play an essential role in mesenchymal-epithelial transition (MET), the key step of nephron generation. Six2, a biological marker related to Wnt signaling pathway, promotes the proliferation, inhibits the apoptosis and maintains the un-differentiation of MM cells. Besides, LiCl is an activator of Wnt signaling pathway. However, the role of LiCl in cellular regulation of MM cells remains unclear, and the relationship between LiCl and Six2 in this process is also little known. Here, we performed EdU assay and flow cytometry assay to, respectively, detect the proliferation and apoptosis of MM cells treated with LiCl of increasing dosages. In addition, reverse transcription-PCR (RT-PCR) and Western-blot were conducted to measure the expression of Six2 and some maker genes of Wnt and bone-morphogenetic-protein (BMP) signaling pathway. Furthermore, luciferase assay was also carried out to detect the transcriptional regulation of Six2. Then we found LiCl promoted MM cell proliferation at low-concentration (10, 20, 30, and 40 mM). The expression of Six2 was dose-dependently increased in low-concentration (10, 20, 30, and 40 mM) at both mRNA and protein level. In addition, both of cell proliferation and Six2 expression in MM cells declined when dosage reached high-concentration (50 mM). However, Six2 knock-down converted the proliferation reduction at 50 mM. Furthermore, Six2 deficiency increased the apoptosis of MM cells, compared with negative control cells at relative LiCl concentration. However, the abnormal rise of apoptosis at 30 mM of LiCl concentration implies that it might be the reduction of GSK3ß that increased cell apoptosis. Together, these demonstrate that LiCl can induce the proliferation and apoptosis of MM cells coordinating with Six2.

[A genome-wide association study on body weight traits of Jinghai yellow chicken].

Body weight traits are important economic characters of broilers. This study was carried out to screen for molecular markers and candidate genes that can be used to improve the body weight traits. A herd of 400 female Jinghai yellow chickens were measured for body weights from 0 to 14 weeks of age. Genome-wide association study (GWAS) was carried out using specific-locus amplified fragment sequencing (SLAF-seq) technology to detect SNPs associated with body weight traits of Jinghai yellow chicken. Finally, 100 SNPs that associated with body weight traits were detected. The results showed that effects of 15 SNPs reached 5% Bonferroni genome-wide significance and 85 SNPs reached potential genome-wide significance. Genes in the candidate regions with 1 Mb windows (SNP position±0.5 Mb) surrounding each significant SNP were screened. Finally, nine candidate genes were obtained, among which four genes of FAM124A (Family with sequence similarity 124A), QDPR (Quinoid dihydropteridine reductase), WDR1 (WD repeat domain 1) and SLC2A9 (Solute carrier family 2 (facilitated glucose transporter), member 9) might be important candidate genes influencing body weight traits of Jinghai yellow chicken. Furthermore, it was also found that most SNPs associated with mid and late growth and body weights were intensively located in the region of 75.6-80.7 Mb on chromosome 4. Our study thus provides a basis for genetic understanding of the Jinghai yellow chicken body weight traits.

Bridging Locomotion and Manipulation Using Reconfigurable Robotic Limbs via Reinforcement Learning.

Locomotion and manipulation are two essential skills in robotics but are often divided or decoupled into two separate problems. It is widely accepted that the topological duality between multi-legged locomotion and multi-fingered manipulation shares an intrinsic model. However, a lack of research remains to identify the data-driven evidence for further research. This paper explores a unified formulation of the loco-manipulation problem using reinforcement learning (RL) by reconfiguring robotic limbs with an overconstrained design into multi-legged and multi-fingered robots. Such design reconfiguration allows for adopting a co-training architecture for reinforcement learning towards a unified loco-manipulation policy. As a result, we find data-driven evidence to support the transferability between locomotion and manipulation skills using a single RL policy with a multilayer perceptron or graph neural network. We also demonstrate the Sim2Real transfer of the learned loco-manipulation skills in a robotic prototype. This work expands the knowledge frontiers on loco-manipulation transferability with learning-based evidence applied in a novel platform with overconstrained robotic limbs.

Dual fluorination of polymer electrolyte and conversion-type cathode for high-capacity all-solid-state lithium metal batteries.

All-solid-state batteries are appealing electrochemical energy storage devices because of their high energy content and safety. However, their practical development is hindered by inadequate cycling performances due to poor reaction reversibility, electrolyte thickening and electrode passivation. Here, to circumvent these issues, we propose a fluorination strategy for the positive electrode and solid polymeric electrolyte. We develop thin laminated all-solid-state Li||FeF3 lab-scale cells capable of delivering an initial specific discharge capacity of about 600 mAh/g at 700 mA/g and a final capacity of about 200 mAh/g after 900 cycles at 60 °C. We demonstrate that the polymer electrolyte containing AlF3 particles enables a Li-ion transference number of 0.67 at 60 °C. The fluorinated polymeric solid electrolyte favours the formation of ionically conductive components in the Li metal electrode's solid electrolyte interphase, also hindering dendritic growth. Furthermore, the F-rich solid electrolyte facilitates the Li-ion storage reversibility of the FeF3-based positive electrode and decreases the interfacial resistances and polarizations at both electrodes.

ID1 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Deterioration of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers in the world. Our aim is to identify prognostic biomarkers that contribute to the progression of early stage ccRCC and clarify the mechanism. Here, the mRNA microarray expression profile of ccRCC samples was obtained from Gene Expression Omnibus (GEO) (GSE68417). 62 differentially expressed genes (DEGs) were gained by R Studio, including 31 upregulated genes and 31 downregulated genes. Pathway enrichment analysis was performed in DAVID database. Then, the protein-protein interaction network was obtained through STRING database and visualized by Cytoscape. Subsequently, among the network, only inhibitor of DNA Binding 1 (ID1) was significant between low-grade and high-grade ccRCC patients in TCGA data set. After analysis of the corresponding clinical information in R Studio, it is shown that low ID1 expression correlated with poor survival, high probability of tumor metastasis, and relatively high serum calcium. Later, functional enrichment of ID1 in GeneMANIA uncovered that regulating DNA binding is a main characteristic of ID1 in ccRCC, which was validated by Kaplan-Meier curve of ID1 associated genes using KM plotter database and R Studio. Immune infiltration analysis performed by Tumor Immune Estimation Resource (TIMER) revealed that CD8+ T cells and macrophages were prognostic factors. Furthermore, Valproic acid was analyzed to be the most convinced target drug of ID1 identified by Comparative Toxicogenomics Database (CTD). Taken together, ID1, a biomarker of clinical outcome in early stage ccRCC patients, has the potential function of preventing deterioration in ccRCC progression and metastasis.

[PPP3CA silence regulates MET process, cell apoptosis, proliferation and migration in metanephric mesenchyme cells].

Kidney is one of the most important organs of the body and the mammalian kidney development is essential for kidney unit formation. The key process of kidney development is metanephric development, where mesenchymal-epithelial transition (MET) plays a crucial role. Here we investigated the biological function of PPP3CA in metanephric mesenchyme (MM) cells. qRT-PCR and Western blotting were used to detect PPP3CA and MET makers expression in mK3, mK4 cells respectively at mRNA and protein level. Subsequently, PPP3CA was stably knocked down via lentivirus infection in mK4 cells. Flow cytometry, EdU/CCK-8 assay, wound healing assay were conducted to clarify the regulation of PPP3CA on cell apoptosis, proliferation and migration respectively. PPP3CA was expressed higher in epithelial-like mK4 cells than mesenchyme-like mK3 cells. Thus, PPP3CA was silenced in mK4 cells and PPP3CA deficiency promoted E-cadherin expression, cell apoptosis. Moreover, PPP3CA knock down attenuated cell proliferation and cell migration in mK4 cell. The underlying mechanism was associated with the dephosphorylation of PPP3CA on ERK1/2. Taken together, our results indicated that PPP3CA mediated MET process and cell behaviors of MM cells, providing new foundation for analyzing potential regulator in kidney development process.

A1CF-Axin2 signal axis regulates apoptosis and migration in Wilms tumor-derived cells through Wnt/ß-catenin pathway.

A1CF, a complementary factor of APOBEC-1, is involved in many cellular processes for its mRNA editing role, such as cell proliferation, apoptosis, and migration. Here, we explored the regulatory function of A1CF in Wilms tumor-derived cells. Quantitative real-time PCR was performed to detect the mRNA level of A1CF, Axin2, ß-Catenin, CCND1 or NKD1 in A1CF-depleted or A1CF-overexpression G401 cells. Western bolt was used to analyze the expression of A1CF, Axin2, and ß-catenin protein. The cell apoptosis and migration ability were determined using flow cytometry assay or wound healing, respectively. Our study demonstrated that overexpression of A1CF, Axin2 was upregulated and knockdown of A1CF decreased Axin2 expression at mRNA and protein levels in G401 cells. Besides, knockdown of A1CF further upregulated ß-catenin, the classical regulator of Wnt signal pathway, and increased CCND1 and NKD1, the target genes of Wnt/ß-catenin. Furthermore, overexpression of Axin2 partly rescued the expression of ß-catenin in A1CF-deficiency stable G401 cells. In Wnt agonist BML-284 treated G401 cells, A1CF was increased like other classical regulator of Wnt signal pathway, such as Axin2 and ß-catenin. Meanwhile, knockdown of Axin2 rescued ß-catenin expression which was decreased in A1CF overexpression condition with BML-284. Further, overexpression of A1CF reduced cell apoptosis but promoted cell migration, and overexpression of Axin2 got similar results. In A1CF-decreased stable G401 cells, overexpression of Axin2 partly rescued the cell apoptosis and migration. We find that A1CF is a positive regulator of Axin2, a Wnt/ß-catenin pathway inhibitor, and A1CF-Axin2 signal axis regulates Wilms tumor-derived cells' apoptosis and migration through Axin2.

Correction to: A1CF-Axin2 signal axis regulates apoptosis and migration in Wilms tumor-derived cells through Wnt/ß-catenin pathway.

In their paper "A1CF-Axin2 signal axis regulates apoptosis and migration in Wilms tumor-derived cells through Wnt/ß-catenin pathway" (In Vitro Cell. Devel. Biol. Anim. 55: 252-259, 2019) Ni et al., regarded the G-401 cell line as being derived from a Wilms' tumor.

Heritability of human visual contour integration-an integrated genomic study.

Contour integration, a key visual function to deal with occlusion and discontinuity in natural scenes, is essential to human survival. However, individuals are not equally well equipped with this ability. In particular, contour integration deficiencies are commonly detected in patients with mental disorders, especially schizophrenia. To understand the underlying sources of these individual differences, the current study investigated the genetic basis of contour integration in humans. A total of 2619 normal participants were tested on their ability to detect continuous contours embedded in a cluttered background. Quantitative genomic analysis was performed, involving heritability estimation based on single nucleotide polymorphisms (SNPs) and association testing at SNP, gene, and pathway levels. Heritability estimation showed that common SNPs contributed 49.5% (standard error of the mean = 15.6%) of overall phenotypic variation, indicating moderate heritability of contour integration. Two-stage genome-wide association analysis (GWAS) detected four SNPs reaching genome-wide significance in the discovery test (N = 1931) but not passing the replication test (N = 688). Gene-level analysis further revealed a significant genome-wide association of a microRNA-encoding gene MIR1178 in both the discovery and replication cohorts. Another gene poly(A)-binding protein nuclear 1 like, cytoplasmic (PABPN1L) showed suggestive significance in the discovery cohort (p < 1 × 10-4) and was replicated in the replication cohort (p = 0.009). The pathway analysis did not detect any significant pathway. Taken together, this study identified significant gene associations with contour integration and provided support for a genetic transmission of the ability to perceive continuous contours in the environment.

PPARG Negatively Modulates Six2 in Tumor Formation of Clear Cell Renal Cell Carcinoma.

Substantial research has revealed that peroxisome proliferator-activated receptor-gamma (PPARG) plays a critical role in glucose homeostasis and lipid metabolism, and recent studies have shown different effects in the progression of different tumors. However, the role of PPARG and its target gene in clear cell renal cell carcinoma (ccRCC) are incompletely understood. Clinical data revealed abnormal glucolipid metabolism in primary ccRCC samples. In addition, transcriptional profiling indicated that PPARG expression was positively correlated, whereas Six2 expression was negatively correlated with the overall survival of ccRCC patients. Staining showed that PPARG was mainly expressed in tumor cell cytoplasm, and Six2 was localized to the nuclei. In a ccRCC cell line, PPARG activation promoted cell apoptosis, inhibited cell migration and proliferation, and reduced Six2 expression. Mechanistically, overexpressing Six2 downregulated E-cadherin expression and cell apoptosis, but PPARG activation reversed those effects. Taken together, PPARG promotes apoptosis and suppresses the migration and proliferation of ccRCC cells by inhibiting Six2. These findings reveal that the PPARG/Six2 axis acts as a central pathobiological mediator of ccRCC formation and as a potential therapeutic target for the treatment of patients with ccRCC.

BMP7 plays a critical role in TMEM100-inhibited cell proliferation and apoptosis in mouse metanephric mesenchymal cells in vitro.

Kidney mainly arises from the induction of metanephric mesenchymal cells (MM cells) and the ureteric bud (UB). Transmembrane protein-100 (Tmem100) consists of two transmembrane regions with strong temporal and spatial expression characteristics during renal development. However, the function of Tmem100 in mouse embryonic kidney-derived cells remained unclear. We provided qPCR to verify the relationship between Tmem100 and the BMP signal pathway. To clarify the role of Tmem100 in cell proliferation and apoptosis, we carry out EdU incorporation, annexin V- fluorescein isothiocyanate (FITC) apoptosis assay. Here, we find that the knockdown of Tmem100 increases the proliferation and apoptosis of mouse embryonic kidney-derived cells, and this promotion can be inhibited by knockdown of BMP7 at the same time; these results suggest that BMP7 plays a crucial role in Tmem100-regulated cell proliferation and apoptosis. qRT-PCR results further demonstrate that the deficiency of Tmem100 leads to BMP7 upregulation and overexpression could get opposite results. In BMP7-depleted MK3 cells, Tmem100 is highly upregulated and BMPR-II is downregulated. And in BMP7-overexpressed MK3 cells, the expression of Tmem100 is decreased. In BMPR-II-depleted MK3 cells, Tmem100 is downregulated and BMP7 expression remains still. These findings indicate that both BMP7 and BMPR-II can regulate Tmem100 and vice versa, and BMPR-II expression is regulated by BMP7. However, BMP7 has no association with BMPR-II in MK3 cells. Our data demonstrated the significant role of BMP7 in Tmem100-regulated cell proliferation and apoptosis and revealed the complicated regulation network among Tmem100, BMP7, and BMPR-II in mouse embryonic kidney-derived cells.

Inflammatory genes are novel prognostic biomarkers for colorectal cancer.

Inflammatory genes serve a crucial role in the pathogenesis of inflammation­associated tumors. However, as recent studies have mainly focused on the effects of single inflammatory genes on colorectal cancer (CRC), but not on the global interactions between genes, the underlying mechanisms between inflammatory genes and CRC remain unclear. In the current study, two inflammation­associated networks were constructed based on inflammatory genes, differentially expressed genes (DEGs) in CRC vs. normal samples, and protein­protein interactions (PPIs). These networks included an inflammation­related neighbor network (IRNN) and an inflammation­related DEG network (IRDN). Notably, the results indicated that the inflammatory genes served as important CRC­associated genes in the IRNN. Certain inflammatory genes were more likely to be network hubs and exhibited higher betweenness centralities, indicating that these inflammatory hub genes had central roles in the communication between genes in the IRNN. By contrast, in the IRDN, functional enrichment analysis revealed that genes were enriched in numerous cancer­associated functions and pathways. Subsequently, 14 genes in a module were identified in the IRDN as the potential biomarkers associated with disease­free survival (DFS) in CRC patients in the GSE24550 dataset, the prognosis of which was further validated using three independent datasets (GSE24549, GSE34551 and GSE103479). All 14 genes (including BCAR1, CRK, FYN, GRB2, LCP2, PIK3R1, PLCG1, PTK2, PTPN11, PTPN6, SHC1, SOS1, SRC and SYK) in this module were inflammatory genes, emphasizing the critical role of inflammation in CRC. In conclusion, these findings based on integrated inflammation­associated networks provided a novel insight that may help elucidate the inflammation­mediated mechanisms involved in CRC.

Multi-level genomic analyses suggest new genetic variants involved in human memory.

Development of high-throughput genotyping platforms provides an opportunity to identify new genetic elements related to complex cognitive functions. Taking advantage of multi-level genomic analysis, here we studied the genetic basis of human short-term (STM, n = 1623) and long-term (LTM, n = 1522) memory functions. Heritability estimation based on single nucleotide polymorphism showed moderate (61%, standard error 35%) heritability of short-term memory but almost zero heritability of long-term memory. We further performed a two-step genome-wide association study, but failed to find any SNPs that could pass genome-wide significance and survive replication at the same time. However, suggestive significance for rs7011450 was found in the shared component of the two STM tasks. Further inspections on its nearby gene zinc finger and at-hook domain containing and SNPs around this gene showed suggestive association with STM. In LTM, a polymorphism within branched chain amino acid transaminase 2 showed suggestive significance in the discovery cohort and has been replicated in another independent population of 1862. Furthermore, we performed a pathway analysis based on the current genomic data and found pathways including mTOR signaling and axon guidance significantly associated with STM capacity. These findings warrant further replication in other larger populations.