Patterns of selective constraints in noncoding DNA of rice

<p>Abstract</p> <p>Background</p> <p>Several studies have investigated the relationships between selective constraints in introns and their length, GC content and location within genes. To date, however, no such investigation has been done in plants. Studies of selective constraints in noncoding DNA have generally involved interspecific comparisons, under the assumption of the same selective pressures acting in each lineage. Such comparisons are limited to cases in which the noncoding sequences are not too strongly diverged so that reliable sequence alignments can be obtained. Here, we investigate selective constraints in a recent segmental duplication that includes 605 paralogous intron pairs that occurred about 7 million years ago in rice (<it>O. sativa</it>).</p> <p>Results</p> <p>Our principal findings are: (1) intronic divergence is negatively correlated with intron length, a pattern that has previously been described in <it>Drosophila </it>and mammals; (2) there is a signature of strong purifying selection at splice control sites; (3) first introns are significantly longer and have a higher GC content than other introns; (4) the divergences of first and non-first introns are not significantly different from one another, a pattern that differs from <it>Drosophila </it>and mammals; and (5) short introns are more diverged than four-fold degenerate sites suggesting that selection reduces divergence at four-fold sites.</p> <p>Conclusion</p> <p>Our observation of stronger selective constraints in long introns suggests that functional elements subject to purifying selection may be concentrated within long introns. Our results are consistent with the presence of strong purifying selection at splicing control sites. Selective constraints are not significantly stronger in first introns of rice, as they are in other species.</p

Selection and mutation on microRNA target sequences during rice evolution

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) posttranscriptionally down-regulate gene expression by binding target mRNAs. Analysis of the evolution of miRNA binding sites is helpful in understanding the co-evolution between miRNAs and their targets. To understand this process in plants a comparative analysis of miRNA-targeted duplicated gene pairs derived from a well-documented whole genome duplication (WGD) event in combination with a population genetics study of six experimentally validated miRNA binding sites in rice (<it>O. sativa</it>) was carried out.</p> <p>Results</p> <p>Of the 1,331 pairs of duplicate genes from the WGD, 41 genes (29 pairs) were computationally predicted to be miRNA targets. Sequence substitution analysis indicated that the synonymous substitution rate was significantly lower in the miRNA binding sites than their 5' and 3' flanking regions. Of the 29 duplicated gene pairs, 17 have only one paralog been targeted by a miRNA. This could be due to either gain of a miRNA binding site after the WGD or because one of the duplicated genes has escaped from being a miRNA target after the WGD (loss of miRNA binding site). These possibilities were distinguished by separating miRNAs conserved in both dicots and monocot plants from rice-specific miRNAs and by phylogenetic analysis of miRNA target gene families. The gain/loss rate of miRNA binding sites was estimated to be 3.0 × 10^-9gain/loss per year. Most (70.6%) of the gains/losses were due to nucleotide mutation. By analysis of cultivated (<it>O. sativa</it>; <it>n </it>= 30) and wild (<it>O. rufipogon</it>; <it>n </it>= 15) rice populations, no segregating site was observed in six miRNA binding sites whereas 0.12–0.20 SNPs per 21-nt or 1.53–1.80 × 10^-3of the average pairwise nucleotide diversity (π) were found in their flanking regions.</p> <p>Conclusion</p> <p>Both molecular evolution and population genetics support the hypothesis that conservation of miRNA binding sites is maintained by purifying selection through elimination of deleterious alleles. Nucleotide mutations play a major role in the gain/loss of miRNA binding sites during evolution.</p

Long intergenic non-coding RNA expression signature in human breast cancer

Breast cancer is a complex disease, characterized by gene deregulation. There is less systematic investigation of the capacity of long intergenic non-coding RNAs (lincRNAs) as biomarkers associated with breast cancer pathogenesis or several clinicopathological variables including receptor status and patient survival. We designed a two-stage study, including 1,000 breast tumor RNA-seq data from The Cancer Genome Atlas (TCGA) as the discovery stage, and RNA-seq data of matched tumor and adjacent normal tissue from 50 breast cancer patients as well as 23 normal breast tissue from healthy women as the replication stage. We identified 83 lincRNAs showing the significant expression changes in breast tumors with a false discovery rate (FDR) < 1% in the discovery dataset. Thirty-seven out of the 83 were validated in the replication dataset. Integrative genomic analyses suggested that the aberrant expression of these 37 lincRNAs was probably related with the expression alteration of several transcription factors (TFs). We observed a differential co-expression pattern between lincRNAs and their neighboring genes. We found that the expression levels of one lincRNA (RP5-1198O20 with Ensembl ID ENSG00000230615) were associated with breast cancer survival with P < 0.05. Our study identifies a set of aberrantly expressed lincRNAs in breast cancer

UDTIRI: An Open-Source Road Pothole Detection Benchmark Suite

It is seen that there is enormous potential to leverage powerful deep learning methods in the emerging field of urban digital twins. It is particularly in the area of intelligent road inspection where there is currently limited research and data available. To facilitate progress in this field, we have developed a well-labeled road pothole dataset named Urban Digital Twins Intelligent Road Inspection (UDTIRI) dataset. We hope this dataset will enable the use of powerful deep learning methods in urban road inspection, providing algorithms with a more comprehensive understanding of the scene and maximizing their potential. Our dataset comprises 1000 images of potholes, captured in various scenarios with different lighting and humidity conditions. Our intention is to employ this dataset for object detection, semantic segmentation, and instance segmentation tasks. Our team has devoted significant effort to conducting a detailed statistical analysis, and benchmarking a selection of representative algorithms from recent years. We also provide a multi-task platform for researchers to fully exploit the performance of various algorithms with the support of UDTIRI dataset.Comment: Database webpage: https://www.udtiri.com/, Kaggle webpage: https://www.kaggle.com/datasets/jiahangli617/udtir

Chitosan-Alginate Sponge: Preparation and Application in Curcumin Delivery for Dermal Wound Healing in Rat

A biodegradable sponge, composed of chitosan (CS) and sodium alginate (SA), was successfully obtained in this work. The sponge was ethereal and pliable. The chemical structure and morphology of the sponges was characterized by FTIR and SEM. The swelling ability, in vitro drug release and degradation behaviors, and an in vivo animal test were employed to confirm the applicability of this sponge as a wound dressing material. As the chitosan content in the sponge decreased, the swelling ability decreased. All types of the sponges exhibited biodegradable properties. The release of curcumin from the sponges could be controlled by the crosslinking degree. Curcumin could be released from the sponges in an extended period for up to 20 days. An in vivo animal test using SD rat showed that sponge had better effect than cotton gauze, and adding curcumin into the sponge enhanced the therapeutic healing effect

Assessment of codivergence of Mastreviruses with their plant hosts

Background: Viruses that have spent most of their evolutionary time associated with a single host lineage should have sequences that reflect codivergence of virus and host. Several examples for RNA viruses of host-virus tree congruence are being challenged. DNA viruses, such as mastreviruses, are more likely than RNA viruses to have maintained a record of host lineage association.Results: The full genomes of 28 isolates of Wheat dwarf virus (WDV), a member of the Mastrevirus genus, from different regions of China were sequenced. The analysis of these 28 entire genomes and 18 entire genome sequences of cereal mastreviruses from other countries support the designation of wheat, barley and oat mastrevirus isolates as separate species. They revealed that relative divergence times for the viruses WDV, Barley dwarf virus (BDV), Oat dwarf virus (ODV) and Maize streak virus (MSV) are proportional to divergence times of their hosts, suggesting codivergence. Considerable diversity among Chinese isolates was found and was concentrated in hot spots in the Rep A, SIR, LIR, and intron regions in WDV genomes. Two probable recombination events were detected in Chinese WDV isolates. Analysis including further Mastrevirus genomes concentrated on coding regions to avoid difficulties due to recombination and hyperdiversity. The analysis demonstrated congruence of trees in two branches of the genus, but not in the third. Assuming codivergence, an evolutionary rate of 10-8 substitutions per site per year was calculated. The low rate implies stronger constraints against change than are obtained by other methods of estimating the rate.Conclusion: We report tests of the hypothesis that mastreviruses have codiverged with their monocotyledonous hosts over 50 million years of evolution. The tests support the hypothesis for WDV, BDV and ODV, but not for MSV and other African streak viruses.Peer reviewedBiochemistry and Molecular Biolog

Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk.

A small number of circulating proteins have been reported to be associated with breast cancer risk, with inconsistent results. Herein, we attempted to identify novel protein biomarkers for breast cancer via the integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large-scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse-variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin-like growth factor receptor 1 and other membrane receptors (OR: 0.82-1.18, p values: 6.96 × 10-4 -3.28 × 10-8 ), are linked to insulin resistance and estrogen receptor signaling pathways. Proteins identified at other loci include those involved in biological processes such as alcohol and lipid metabolism, proteolysis, apoptosis, immune regulation and cell motility and proliferation. Consistent associations were observed for 22 proteins in the UK Biobank data (p < 0.05). The study identifies potential novel biomarkers for breast cancer, but further investigation is needed to replicate our findings.Includes CRUK and FP7

Characterization of the past and current duplication activities in the human 22q11.2 region

<p>Abstract</p> <p>Background</p> <p>Segmental duplications (SDs) on 22q11.2 (LCR22), serve as substrates for meiotic non-allelic homologous recombination (NAHR) events resulting in several clinically significant genomic disorders.</p> <p>Results</p> <p>To understand the duplication activity leading to the complicated SD structure of this region, we have applied the A-Bruijn graph algorithm to decompose the 22q11.2 SDs to 523 fundamental duplication sequences, termed subunits. Cross-species syntenic analysis of primate genomes demonstrates that many of these LCR22 subunits emerged very recently, especially those implicated in human genomic disorders. Some subunits have expanded more actively than others, and young <it>Alu </it>SINEs, are associated much more frequently with duplicated sequences that have undergone active expansion, confirming their role in mediating recombination events. Many copy number variations (CNVs) exist on 22q11.2, some flanked by SDs. Interestingly, two chromosome breakpoints for 13 CNVs (mean length 65 kb) are located in paralogous subunits, providing direct evidence that SD subunits could contribute to CNV formation. Sequence analysis of PACs or BACs identified extra CNVs, specifically, 10 insertions and 18 deletions within 22q11.2; four were more than 10 kb in size and most contained young <it>AluY</it>s at their breakpoints.</p> <p>Conclusions</p> <p>Our study indicates that <it>AluY</it>s are implicated in the past and current duplication events, and moreover suggests that DNA rearrangements in 22q11.2 genomic disorders perhaps do not occur randomly but involve both actively expanded duplication subunits and <it>Alu </it>elements.</p

A Large Gene Network in Immature Erythroid Cells Is Controlled by the Myeloid and B Cell Transcriptional Regulator PU.1

PU.1 is a hematopoietic transcription factor that is required for the development of myeloid and B cells. PU.1 is also expressed in erythroid progenitors, where it blocks erythroid differentiation by binding to and inhibiting the main erythroid promoting factor, GATA-1. However, other mechanisms by which PU.1 affects the fate of erythroid progenitors have not been thoroughly explored. Here, we used ChIP-Seq analysis for PU.1 and gene expression profiling in erythroid cells to show that PU.1 regulates an extensive network of genes that constitute major pathways for controlling growth and survival of immature erythroid cells. By analyzing fetal liver erythroid progenitors from mice with low PU.1 expression, we also show that the earliest erythroid committed cells are dramatically reduced in vivo. Furthermore, we find that PU.1 also regulates many of the same genes and pathways in other blood cells, leading us to propose that PU.1 is a multifaceted factor with overlapping, as well as distinct, functions in several hematopoietic lineages