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Peng Yu

Publications and source records attributed to Peng Yu.

At least 19 recordsLinked to original sources

The MexMAGIC population reveals the genetic architecture of traits exhibiting clinal variation in Mexican native maize.

Defining the genetic basis of local adaptation is a key goal of evolutionary biology and crop improvement. Theory predicts that when selective pressures follow differences in the environment, a cline will be established. Clines can be exploited to uncover adaptive variation by association of alleles with the environment. However, monotonic phenotypic change over a cline is not necessarily mirrored in the behavior of genetic variants and population structure can further complicate analysis. To study genetic and phenotypic variation across the environment, we developed a multi-parent advanced generation inter-cross (MAGIC) population using eight Mexican native maize (Zea mays L. ssp. mays) varieties sourced from distinct agroecological zones. We evaluated the population in a common garden in Mexico and mapped tassel branching and flowering time, two traits that exhibit clinal variation. Variation in tassel branching was dominated by a single QTL with allele effects aligning to a negative elevational cline. By contrast, allele effects associated with 11 identified flowering time QTL were not consistently correlated with any one source environmental factor. Our observations support the prediction that genotype-environment association will be strongest under simple genetic architecture, although, even then, analysis in native populations may be confounded by population structure.

MAGIC↗

Atopic dermatitis and the risk of osteoporosis and fractures: a meta-analysis of cohort studies.

BACKGROUND: This meta-analysis aims to evaluate the risk of osteoporosis and fractures in patients with atopic dermatitis (AD) by synthesizing data from cohort studies. We also provide a comprehensive analysis of fracture risks across different severities of AD and anatomical sites. METHODS: Following the PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Embase, and the Cochrane Library up to May 30, 2025. Studies that investigated the relationship between AD and osteoporosis or fractures were included in the analysis. Data extraction and screening were performed independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was applied, alongside sensitivity and subgroup analyses. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Ten cohort studies, involving 368 to over 2 million AD patients, were included. NOS scores ranged from 7 to 8, indicating generally high study quality. The pooled analysis revealed a 56% increased risk of osteoporosis (OR = 1.56, 95% CI: 1.14-2.13; I2&#xa0;=&#xa0;99.9%, p&#x2009;<&#x2009;0.0001) and an 8% increased risk of all-cause fractures (OR = 1.08, 95% CI: 1.05-1.10; I2&#xa0;=&#xa0;82.1%, p&#x2009;<&#x2009;0.0001) in AD patients. Subgroup analyses demonstrated a progressive increase in fracture risk with the severity of AD. Specific risks were significantly higher for vertebral fractures (OR = 1.14, 95% CI: 1.08-1.20; I2&#xa0;=&#xa0;67.3%, p&#x2009;=&#x2009;0.009) and lower limb fractures (OR = 1.11, 95% CI: 1.08-1.13; I2&#xa0;=&#xa0;65.0%, p&#x2009;=&#x2009;0.014). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected (p&#x2009;=&#x2009;0.316). CONCLUSION: AD is associated with an increased risk of osteoporosis and fractures, particularly among patients with severe AD and those experiencing vertebral or lower limb fractures. These findings highlight the importance of targeted bone health monitoring in the clinical management of AD patients.Registration: (PROSPERO: CRD420251066550).

Humans↗

SURROGATE SELECTION OVERSAMPLES EXPANDED T CELL CLONOTYPES.

Surrogate selection is an experimental design that without sequencing any DNA can restrict a sample of cells to those carrying certain genomic mutations. In immunological disease studies, this design may provide a relatively easy approach to enrich a lymphocyte sample with cells relevant to the disease response because the emergence of neutral mutations associates with the proliferation history of clonal subpopulations. A statistical analysis of clonotype sizes provides a structured, quantitative perspective on this useful property of surrogate selection. Our model specification couples within-clonotype birth-death processes with an exchangeable model across clonotypes. Beyond enrichment questions about the surrogate selection design, our framework enables a study of sampling properties of elementary sample diversity statistics; it also points to new statistics that may usefully measure the burden of somatic genomic alterations associated with clonal expansion. We examine statistical properties of immunological samples governed by the coupled model specification, and we illustrate calculations in surrogate selection studies of melanoma and in single-cell genomic studies of T cell repertoires.

Bayes&#x2019;s rule↗

The possible involvement of endogenous ligands for mu-, delta- and kappa-opioid receptors in modulating morphine-induced CPP expression in rats.

Previous studies suggested that electroacupuncture (EA) can suppress opioid dependence by the release of endogenous opioid peptides. To explore the site of action and the receptors involved, we tried to inject highly specific agonists for mu-, delta- and kappa-opioid receptors into the CNS to test whether it can suppress morphine-induced conditioned place preference (CPP) in the rat. Male Sprague-Dawley rats were trained with 4 mg/kg morphine, i.p. for 4 days to establish the CPP model. This CPP can be prevented by (a) i.p. injection of 3 mg/kg dose of morphine, (b) intracerebroventricular (i.c.v.) injection of micrograms doses of the selective mu-opioid receptor agonist DAMGO, delta-agonist DPDPE or kappa-agonist U-50,488H or (c) microinjection of DAMGO, DPDPE or U50488H into the shell of the nucleus accumbens (NAc). The results suggest that the release of endogenous mu-, delta- and kappa-opioid agonists in the NAc shell may play a role for EA suppression of opiate addiction.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Isolation and characterization of coactivator-binding peptoids from a combinatorial library.

Pharmacologic agents capable of activating the expression of specific genes would be valuable tools in biological research and could potentially be useful therapeutically. Efforts to develop a general solution to this problem have focused on the discovery of cell permeable mimics of native transcription factors comprised of linked DNA-binding and activation domain surrogates. Recently, we reported the isolation of a peptoid, called KBPo2, that binds a fragment of the mammalian coactivator CREB-binding protein (CBP). When delivered to a promoter-bound DNA-binding domain, this peptoid acted as a potent activation domain mimic in human cells. In this paper, we provide full details of the screening experiments and also report further characterization of this molecule as well as the other peptoids that came out of the screen. Of the three peptoids identified as putative CBP ligands, only KBPo2 demonstrated the necessary combination of binding affinity, specificity and cell permeability necessary to function as a potent activation domain mimic in cells. KBPo2 binds to CBP in a region different than that recognized by the native activation peptide from the transcription factor CREB.

CREB-Binding Protein↗

High performance liquid chromatography - tandem mass spectrometric determination of cyclovirobuxine D in human plasma.

A sensitive, specific and rapid high performance liquid chromatography - tandem mass spectrometric (LC/MS/MS) method for the determination of cyclovirobuxine D in human plasma was developed and validated. The triple-quadrupole tandem mass spectrometric detector with an electrospray interface (ESI) was operated under the selected reaction monitoring (SRM) mode. After the addition of citalopram as an internal standard (IS), plasma samples were extracted with ethyl acetate. Chromatographic separation of the analytes was performed on a Kromasil CN column with a mobile phase of methanol/water (88/12, v/v) containing 0.4% formic acid. Linearity was established for the range of concentration 0.2-40ng/ml. Under optimized conditions, the mean recovery was 86.6%. The intra-day precision ranged from 4.56% to 7.81%, while the intra-day accuracy ranged from 2.75% to 11.0%. The inter-day precision was in the range 3.87-10.7%, and the inter-day accuracy was in the range -4.00% to 2.50%. The cyclovirobuxine D was stable in human plasma after three freeze-thaw cycles, under storage at room temperature for 12h, in a freezer at -20 degrees C for 15 days and during processing (in autosampler) at 10 degrees C for 24h. The validated method is suitable for quantitative determination of cyclovirobuxine D in human plasma in pharmacokinetics study and has been successfully applied to the analysis of clinical samples.

Adolescent↗

Cell-based screening and validation of human novel genes associated with cell viability.

In the present study, a cell-based high-throughput assay is established to identify novel human genes associated with cell viability. The assay relies on the down-regulation of Renilla luciferase (pRL) activity in a 96-well format. In addition, 2-color fluorescence probes were used to distinguish living and dead cells. As the positive control, the authors used the expression vectors encoding Bax, TNFRSF1A, and TAJ, which were widely known to effectively induce programmed cell death. They screened 409 novel genes (including alternative mRNA splicing forms) cloned in their laboratory and found that 39 genes could significantly down-regulate pRL activity. A subsequent fluorescence-based assay revealed that 4 of the 39 genes (PIP5KL1, OLFM1, RNF122, FAM26B) were associated with cell viability. Further function assays validated that the 4 genes were able to induce both necrosis and apoptosis. These results therefore indicate that a rapid and effective screening system has been developed, which should shed light on some functions of novel genes.

Apoptosis↗

The role of NR2B containing NMDA receptor in place preference conditioned with morphine and natural reinforcers in rats.

It has been reported that N-methyl-D-aspartate (NMDA) receptor is implicated in drug addiction and antagonists of the NMDA receptor complex can inhibit the development and expression of conditioned place preference (CPP) induced by several addictive drugs, implying that this class of compounds might be considered as candidate for the treatment of substance abuse. To explore this possibility, it is important to evaluate whether the inhibitory effect of NMDA receptor antagonists would be confined to behaviors produced by drugs of abuse only, but not by natural reinforcers. According to the quantitative changes of NMDA receptor subunits, including NR1, NR2A, and NR2B, induced by diverse types of reinforcers, we chose NR2B subunit as the target of research. Experimental results showed that (1) an augmented expression of NR2B subunit was revealed by Western blotting in the nucleus accumbens (NAc) and the hippocampus in rats with CPP induced by morphine, but not by natural rewards such as food, novel environment and social interaction. (2) Ifenprodil, an antagonist highly selective for NR2B subunit of the NMDA receptor, produced a dose-dependent reduction in CPP induced by morphine and novel environment, but not that by food consumption and social interaction. Taking together, these findings suggested that NR2B containing NMDA receptor may be more involved with morphine reward rather than natural rewards, and that antagonism of NR2B may have a potential for the treatment of morphine abuse.

Analysis of Variance↗

Mass transport and shear stress in a microchannel bioreactor: numerical simulation and dynamic similarity.

Microchannel bioreactors have been used in many studies to manipulate and investigate the fluid microenvironment around cells. In this study, substrate concentrations and shear stresses at the base were computed from a three-dimensional numerical flow-model incorporating mass transport. Combined dimensionless parameters were developed from a simplified analysis. The numerical results of substrate concentration were well correlated by the combined parameters. The generalized results may find applications in design analysis of microchannel bioreactors. The mass transport and shear stress were related in a generalized result. Based on the generalized results and the condition of dynamic similarity, various means to isolate their respective effects on cells were considered.

Animals↗

Simple reporter gene-based assays for hairpin poly(amide) conjugate permeability and DNA-binding activity in living cells.

Hairpin poly(amide)s (HPs) are sequence specific DNA-binding compounds that have engendered considerable interest as potential pharmacological agents to manipulate the expression of specific genes. However, recent reports have indicated that the ability of HP conjugates to pass through cell membranes is sensitive to the cell type employed and the nature of the conjugate. Furthermore, while binding of HPs to DNA sequences in vitro is relatively well understood, packing of DNA into chromatin in living cells makes predicting the efficiency with which a given poly(amide) will bind its cognate site less certain. Previous methods to evaluate HP permeability and binding in vivo, while effective, are somewhat tedious and qualitative. We report here two related reporter gene-based assays that provide a more convenient and quantitative measure of poly(amide) permeability and DNA binding activity in living cells. We anticipate that these methods will complement existing tools and facilitate the development of HP conjugates with the desired biological activity.

Base Sequence↗

A potent transactivation domain mimic with activity in living cells.

Transcriptional coactivator-binding peptoids were isolated from a large combinatorial library. One of these molecules is shown to function as a potent activation domain surrogate in mammalian cells. Up to a 900-fold increase in expression of a Gal4-responsive reporter gene is observed when a steroid conjugate of the peptoid is incubated with HeLa cells expressing a Gal4 DNA-binding domain (DBD)-glucocorticoid receptor ligand-binding domain (GRLBD) fusion protein.

Animals↗

A high-throughput assay for assessing the cell permeability of combinatorial libraries.

There is great interest in the identification of synthetic molecules that are capable of manipulating protein-protein interactions in living cells. Peptides, unlike other classes of small molecules, have binding properties appropriate for this application, but most are poorly cell permeable and sensitive to proteases. Therefore, considerable effort has been expended in the development of libraries of oligomeric peptide-like molecules. However, there are no clear-cut rules to guide the design of libraries rich in cell permeable compounds. Furthermore, currently available empirical methods to assess permeability may not accurately reflect true permeability and/or are capable of only modest throughput. We describe here an assay for assessing the relative cell permeability of synthetic molecules in the context of steroid fusions that is capable of high throughput and can be used in any transfectable cell line.

Binding, Competitive↗

Nested genes in the human genome.

Here we studied one special type of gene, i.e., the nested gene, in the human genome. We collected 373 reliably annotated nested genes. Two-thirds of them were on the strand opposite that of their host gene. About 58% coding nested gene pairs were conserved in mouse and some were even maintained in chicken and fish, while nested pseudogenes were poorly conserved. Ka/Ks analysis revealed that nested genes were under strong selection, although they did not demonstrate greater conservation than other genes. With microarray data we observed that two partners of one nested pair seemed to be expressed reciprocally. A significant proportion of nested genes were tissue-specifically expressed. Gene ontology analysis demonstrated that quite a number of nested genes participated in cellular signal transduction. Based on these observations, we think that nested genes are a group of genes with important physiological functions.

Animals↗

Mitogen-activated protein kinases regulate platelet-activating factor-induced hyperpermeability.

OBJECTIVE: The authors tested the hypothesis that p42/44- (ERK-1/2) and/or p38-mitogen-activated protein kinases (MAPK) are in vivo regulatory elements in the platelet-activating factor (PAF) activated signaling cascade that stimulates microvascular hyperpermeability. METHODS: FITC-dextran 70 was used as the macromolecular tracer for microvascular permeability in the mouse mesenteric fat tissue. Interstitial integrated optical intensity (IOI) was used as an index of permeability. RESULTS: An application of 10(-7) M PAF increased IOI from 23.1 +/- 3.6 to 70.8 +/- 7.4 (mean +/- SEM). Inhibition of ERK-1/2 with 3 microM and 30 microM AG126 reduced IOI to 32.3 +/- 2.5. Similarly, inhibition of p38-MAPK with 6 nM, 60 nM and 600 nM SB203580 lowered IOI to 29.1 +/- 2.4. CONCLUSIONS: The results demonstrate that ERK-1/2 and p38MAPK participate in the signaling cascade that regulates PAF-induced microvascular hyperpermeability in vivo.

Animals↗

Comparative study of apoptosis-related gene loci in human, mouse and rat genomes.

Many genes are involved in mammalian cell apoptosis pathway. These apoptosis genes often contain characteristic functional domains, and can be classified into at least 15 functional groups, according to previous reports. Using an integrated bioinformatics platform for motif or domain search from three public mammalian proteomes (International Protein Index database for human, mouse, and rat), we systematically cataloged all of the proteins involved in mammalian apoptosis pathway. By localizing those proteins onto the genomes, we obtained a gene locus centric apoptosis gene catalog for human, mouse and rat. Further phylogenetic analysis showed that most of the apoptosis related gene loci are conserved among these three mammals. Interestingly, about one-third of apoptosis gene loci form gene clusters on mammal chromosomes, and exist in the three species, which indicated that mammalian apoptosis gene orders are also conserved. In addition, some tandem duplicated gene loci were revealed by comparing gene loci clusters in the three species. All data produced in this work were stored in a relational database and may be viewed at http://pcas.cbi.pku.edu.cn/database/apd.php.

Animals↗

PCAS--a precomputed proteome annotation database resource.

BACKGROUND: Many model proteomes or "complete" sets of proteins of given organisms are now publicly available. Much effort has been invested in computational annotation of those "draft" proteomes. Motif or domain based algorithms play a pivotal role in functional classification of proteins. Employing most available computational algorithms, mainly motif or domain recognition algorithms, we set up to develop an online proteome annotation system with integrated proteome annotation data to complement existing resources. RESULTS: We report here the development of PCAS (ProteinCentric Annotation System) as an online resource of pre-computed proteome annotation data. We applied most available motif or domain databases and their analysis methods, including hmmpfam search of HMMs in Pfam, SMART and TIGRFAM, RPS-PSIBLAST search of PSSMs in CDD, pfscan of PROSITE patterns and profiles, as well as PSI-BLAST search of SUPERFAMILY PSSMs. In addition, signal peptide and TM are predicted using SignalP and TMHMM respectively. We mapped SUPERFAMILY and COGs to InterPro, so the motif or domain databases are integrated through InterPro. PCAS displays table summaries of pre-computed data and a graphical presentation of motifs or domains relative to the protein. As of now, PCAS contains human IPI, mouse IPI, and rat IPI, A. thaliana, C. elegans, D. melanogaster, S. cerevisiae, and S. pombe proteome.PCAS is available at http://pak.cbi.pku.edu.cn/proteome/gca.php CONCLUSION: PCAS gives better annotation coverage for model proteomes by employing a wider collection of available algorithms. Besides presenting the most confident annotation data, PCAS also allows customized query so users can inspect statistically less significant boundary information as well. Therefore, besides providing general annotation information, PCAS could be used as a discovery platform. We plan to update PCAS twice a year. We will upgrade PCAS when new proteome annotation algorithms identified.

Algorithms↗