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Biomedical subjects

Tong Zhu

Publications and source records attributed to Tong Zhu.

At least 19 recordsLinked to original sources

Enhancement of secondary organic aerosol formation from isoprene photooxidation by ammonia.

Ammonia (NH3) can participate in atmospheric secondary organic aerosol (SOA) formation by reacting with organic acids and carbonyl compounds in particle phase, but its influence on the gas phase chemistry remains unclear. This study performed a series of smog chamber experiments to investigate the influence of NH3 on the formation of SOA from isoprene photooxidation by OH radicals. Both gas and particle phase products were measured with a series of state-of- art instruments including a nitrate ion chemical ionization mass spectrometer (nitrate-CIMS) and high-resolution time-of-flight aerosol mass spectrometer (HR-TOF-AMS). Our results showed that in the presence of NH3 SOA in the chamber significantly increased, along with an enhanced oxidation of isoprene. CIMS analysis further showed that NH3 in the chamber homogeneously reacts not only with gas-phase organic acids but also with gaseous low volatility oxygenated organic molecules (OOMs) to generate extremely low volatility and ultralow volatility NH3-OOMs clusters. Quantum chemical calculation showed that NH3 can spontaneously interact with OOMs to form NH3-OOMs clusters by forming hydrogen bonds with RCOOH, R-OOH, and R-OH. These clusters can promote new particles formation and particle growth through nucleation and condensation, directly enhancing the isoprene SOA production with a contribution of 78% to the enhanced SOA. Moreover, the formation of NH3-OOMs clusters also results in more isoprene consumed by OH radicals, indirectly increasing the SOA production with a contribution of 22 % to the enhanced SOA. Our work for the first time clarified a synergetic effect of NH3 on isoprene SOA formation, which should be accounted for by models.

Aerosols↗

Expression profiles of Arabidopsis thaliana in mineral deficiencies reveal novel transporters involved in metal homeostasis.

Plants directly assimilate minerals from the environment and thus are key for acquisition of metals by all subsequent consumers. Limited bio-availability of copper, zinc and iron in soil decreases both the agronomic productivity and the nutrient quality of crops. Understanding the molecular mechanisms underlying metal homeostasis in plants is a prerequisite to optimizing plant yield and metal nutrient content. To absorb and maintain a balance of potentially toxic metal ions, plants utilize poorly understood mechanisms involving a large number of membrane transporters and metal binding proteins with overlapping substrate specificities and complex regulation. To better understand the function and the integrated regulation, we analyzed in Arabidopsis the expression patterns in roots and in leaves of 53 genes coding for known or potential metal transporters, in response to copper, zinc, and iron deficiencies in Arabidopsis. Comparative analysis of gene expression profiles revealed specific transcriptional regulation by metals of the genes contrasting with the known wide substrate specificities of the encoded transporters. Our analysis suggested novel transport roles for several gene products and we used functional complementation of yeast mutants to correlate specific regulation by metals with transport activity. We demonstrate that two ZIP genes, ZIP2 and ZIP4, are involved in copper transport. We also present evidence that AtOPT3, a member of the oligopeptide transporter gene family with significant similarities to the maize iron-phytosiderophore transporter YS1, is regulated by metals and heterologous expression AtOPT3 can rescue yeast mutants deficient in metal transport.

Arabidopsis↗

Identification of nutrient partitioning genes participating in rice grain filling by singular value decomposition (SVD) of genome expression data.

BACKGROUND: In order to identify rice genes involved in nutrient partitioning, microarray experiments have been done to quantify genomic scale gene expression. Genes involved in nutrient partitioning, specifically grain filling, will be used to identify other co-regulated genes, and DNA binding proteins. Proper identification of the initial set of bait genes used for further investigation is critical. Hierarchical clustering is useful for grouping genes with similar expression profiles, but decreases in utility as data complexity and systematic noise increases. Also, its rigid classification of genes is not consistent with our belief that some genes exhibit multifaceted, context dependent regulation. RESULTS: Singular value decomposition (SVD) of microarray data was investigated as a method to complement current techniques for gene expression pattern recognition. SVD's usefulness, in finding likely participants in grain filling, was measured by comparison with results obtained previously via clustering. 84 percent of these known grain-filling genes were re-identified after detailed SVD analysis. An additional set of 28 genes exhibited a stronger grain-filling pattern than those grain-filling genes that were unselected. They also had upstream sequence containing motifs over-represented among grain filling genes. CONCLUSIONS: The pattern-based perspective that SVD provides complements to widely used clustering methods. The singular vectors provide information about patterns that exist in the data. Other aspects of the decomposition indicate the extent to which a gene exhibits a pattern similar to those provided by the singular vectors. Thus, once a set of interesting patterns has been identified, genes can be ranked by their relationship with said patterns.

Cluster Analysis↗

Gene expression phenotypes of Arabidopsis associated with sensitivity to low temperatures.

Chilling is a common abiotic stress that leads to economic losses in agriculture. By comparing the transcriptome of Arabidopsis under normal (22 degrees C) and chilling (13 degrees C) conditions, we have surveyed the molecular responses of a chilling-resistant plant to acclimate to a moderate reduction in temperature. The mRNA accumulation of approximately 20% of the approximately 8,000 genes analyzed was affected by chilling. In particular, a highly significant number of genes involved in protein biosynthesis displayed an increase in transcript abundance. We have analyzed the molecular phenotypes of 12 chilling-sensitive mutants exposed to 13 degrees C before any visible phenotype could be detected. The number and pattern of expression of chilling-responsive genes in the mutants were consistent with their final degree of chilling injury. The mRNA accumulation profiles for the chilling-lethal mutants chs1, chs2, and chs3 were highly similar and included extensive chilling-induced and mutant-specific alterations in gene expression. The expression pattern of the mutants upon chilling suggests that the normal function of the mutated loci prevents a damaging widespread effect of chilling on transcriptional regulation. In addition, we have identified 634 chilling-responsive genes with aberrant expression in all of the chilling-lethal mutants. This reference gene list, including genes related to lipid metabolism, chloroplast function, carbohydrate metabolism and free radical detoxification, represents a potential source for genes with a critical role in plant acclimation to suboptimal temperatures. The comparison of transcriptome profiles after transfer of Arabidopsis plants from 22 degrees C to 13 degrees C versus transfer to 4 degrees C suggests that quantitative and temporal differences exist between these molecular responses.

Acclimatization↗

Characterization of the early response of Arabidopsis to Alternaria brassicicola infection using expression profiling.

All tested accessions of Arabidopsis are resistant to the fungal pathogen Alternaria brassicicola. Resistance is compromised by pad3 or coi1 mutations, suggesting that it requires the Arabidopsis phytoalexin camalexin and jasmonic acid (JA)-dependent signaling, respectively. This contrasts with most well-studied Arabidopsis pathogens, which are controlled by salicylic acid-dependent responses and do not benefit from absence of camalexin or JA. Here, mutants with defects in camalexin synthesis (pad1, pad2, pad3, and pad5) or in JA signaling (pad1, coi1) were found to be more susceptible than wild type. Mutants with defects in salicylic acid (pad4 and sid2) or ethylene (ein2) signaling remained resistant. Plant responses to A. brassicicola were characterized using expression profiling. Plants showed dramatic gene expression changes within 12 h, persisting at 24 and 36 h. Wild-type and pad3 plants responded similarly, suggesting that pad3 does not have a major effect on signaling. The response of coi1 plants was quite different. Of the 645 genes induced by A. brassicicola in wild-type and pad3 plants, 265 required COI1 for full expression. It is likely that some of the COI1-dependent genes are important for resistance to A. brassicicola. Responses to A. brassicicola were compared with responses to Pseudomonas syringae infection. Despite the fact that these pathogens are limited by different defense responses, approximately 50% of the induced genes were induced in response to both pathogens. Among these, requirements for COI1 were consistent after infection by either pathogen, suggesting that the regulatory effect of COI1 is similar regardless of the initial stimulus.

Alternaria↗

Crosstalk between cytosolic and plastidial pathways of isoprenoid biosynthesis in Arabidopsis thaliana.

In plants, the formation of isopentenyl diphosphate and dimethylallyl diphosphate, the central intermediates in the biosynthesis of isoprenoids, is compartmentalized: the mevalonate (MVA) pathway, which is localized to the cytosol, is responsible for the synthesis of sterols, certain sesquiterpenes, and the side chain of ubiquinone; in contrast, the recently discovered MVA-independent pathway, which operates in plastids, is involved in providing the precursors for monoterpenes, certain sesquiterpenes, diterpenes, carotenoids, and the side chains of chlorophylls and plastoquinone. Specific inhibitors of the MVA pathway (lovastatin) and the MVA-independent pathway (fosmidomycin) were used to perturb biosynthetic flux in Arabidopsis thaliana seedlings. The interaction between both pathways was studied at the transcriptional level by using GeneChip (Affymetrix) microarrays and at the metabolite level by assaying chlorophylls, carotenoids, and sterols. Treatment of seedlings with lovastatin resulted in a transient decrease in sterol levels and a transient increase in carotenoid as well as chlorophyll levels. After the initial drop, sterol amounts in lovastatin-treated seedlings recovered to levels above controls. As a response to fosmidomycin treatment, a transient increase in sterol levels was observed, whereas chlorophyll and carotenoid amounts decreased dramatically when compared with controls. At 96 h after fosmidomycin addition, the levels of all metabolites assayed (sterols, chlorophylls, and carotenoids) were substantially lower than in controls. Interestingly, these inhibitor-mediated changes were not reflected in altered gene expression levels of the genes involved in sterol, chlorophyll, and carotenoid metabolism. The lack of correlation between gene expression patterns and the accumulation of isoprenoid metabolites indicates that posttranscriptional processes may play an important role in regulating flux through isoprenoid metabolic pathways.

Arabidopsis↗

Global analysis of gene expression using GeneChip microarrays.

DNA microarray technology, especially the use of GeneChip microarrays, has become a standard tool for parallel gene expression analysis. Recent improvements in GeneChip microarrays enable whole-genome expression analysis, and thus open a new avenue for studies of the composition, dynamics, and regulation of the transcriptome in plants.

Computational Biology↗

Diverse RNA viruses elicit the expression of common sets of genes in susceptible Arabidopsis thaliana plants.

Systemic infections of plants by viruses require that viruses modify host cells in order to facilitate infections. These modifications include induction of host factors required for replication, propagation and movement, and suppression of host defense responses, which are likely to be associated with changes in host gene expression. Past studies of the effects of viral infection on gene expression in susceptible hosts have been limited to only a handful of genes. To gain broader insight into the responses elicited by viruses in susceptible hosts, high-density oligonucleotide probe microarray technology was used. Arabidopsis leaves were either mock inoculated or inoculated with cucumber mosaic cucumovirus, oil seed rape tobamovirus, turnip vein clearing tobamovirus, potato virus X potexvirus, or turnip mosaic potyvirus. Inoculated leaves were collected at 1, 2, 4, and 5 days after inoculation, total RNA was isolated, and samples were hybridized to Arabidopsis GeneChip microarrays (Affymetrix). Microarray hybridization revealed co-ordinated changes in gene expression in response to infection by diverse viruses. These changes include virus-general and virus-specific alterations in the expression of genes associated with distinct defense or stress responses. Analyses of the promoters of these genes further suggest that diverse RNA viruses elicit common responses in susceptible plant hosts through signaling pathways that have not been previously characterized.

Arabidopsis↗

Topology of the network integrating salicylate and jasmonate signal transduction derived from global expression phenotyping.

The signal transduction network controlling plant responses to pathogens includes pathways requiring the signal molecules salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). The network topology was explored using global expression phenotyping of wild-type and signaling-defective mutant plants, including eds3, eds4, eds5, eds8, pad1, pad2, pad4, NahG, npr1, sid2, ein2, and coi1. Hierarchical clustering was used to define groups of mutations with similar effects on gene expression and groups of similarly regulated genes. Mutations affecting SA signaling formed two groups: one comprised of eds4, eds5, sid2, and npr1-3 affecting only SA signaling; and the other comprised of pad2, eds3, npr1-1, pad4, and NahG affecting SA signaling as well as another unknown process. Major differences between the expression patterns in NahG and the SA biosynthetic mutant sid2 suggest that NahG has pleiotropic effects beyond elimination of SA. A third group of mutants comprised of eds8, pad1, ein2, and coi1 affected ethylene and jasmonate signaling. Expression patterns of some genes revealed mutual inhibition between SA- and JA-dependent signaling, while other genes required JA and ET signaling as well as the unknown signaling process for full expression. Global expression phenotype similarities among mutants suggested, and experiments confirmed, that EDS3 affects SA signaling while EDS8 and PAD1 affect JA signaling. This work allowed modeling of network topology, definition of co-regulated genes, and placement of previously uncharacterized regulatory genes in the network.

Arabidopsis↗

Large-scale identification of single-feature polymorphisms in complex genomes.

We have developed a high-throughput genotyping platform by hybridizing genomic DNA from Arabidopsis thaliana accessions to an RNA expression GeneChip (AtGenome1). Using newly developed analytical tools, a large number of single-feature polymorphisms (SFPs) were identified. A comparison of two accessions, the reference strain Columbia (Col) and the strain Landsberg erecta (Ler), identified nearly 4000 SFPs, which could be reliably scored at a 5% error rate. Ler sequence was used to confirm 117 of 121 SFPs and to determine the sensitivity of array hybridization. Features containing sequence repeats, as well as those from high copy genes, showed greater polymorphism rates. A linear clustering algorithm was developed to identify clusters of SFPs representing potential deletions in 111 genes at a 5% false discovery rate (FDR). Among the potential deletions were transposons, disease resistance genes, and genes involved in secondary metabolism. The applicability of this technique was demonstrated by genotyping a recombinant inbred line. Recombination break points could be clearly defined, and in one case delimited to an interval of 29 kb. We further demonstrate that array hybridization can be combined with bulk segregant analysis to quickly map mutations. The extension of these tools to organisms with complex genomes, such as Arabidopsis, will greatly increase our ability to map and clone quantitative trait loci (QTL).

Arabidopsis↗

Quantitative nature of Arabidopsis responses during compatible and incompatible interactions with the bacterial pathogen Pseudomonas syringae.

We performed large-scale mRNA expression profiling using an Affymetrix GeneChip to study Arabidopsis responses to the bacterial pathogen Pseudomonas syringae. The interactions were compatible (virulent bacteria) or incompatible (avirulent bacteria), including a nonhost interaction and interactions mediated by two different avirulence gene-resistance (R) gene combinations. Approximately 2000 of the approximately 8000 genes monitored showed reproducible significant expression level changes in at least one of the interactions. Analysis of biological variation suggested that the system behavior of the plant response in an incompatible interaction was robust but that of a compatible interaction was not. A large part of the difference between incompatible and compatible interactions can be explained quantitatively. Despite high similarity between responses mediated by the R genes RPS2 and RPM1 in wild-type plants, RPS2-mediated responses were strongly suppressed by the ndr1 mutation and the NahG transgene, whereas RPM1-mediated responses were not. This finding is consistent with the resistance phenotypes of these plants. We propose a simple quantitative model with a saturating response curve that approximates the overall behavior of this plant-pathogen system.

Algorithms↗

EMF genes maintain vegetative development by repressing the flower program in Arabidopsis.

The EMBRYONIC FLOWER (EMF) genes EMF1 and EMF2 are required to maintain vegetative development and repress flower development. EMF1 encodes a putative transcriptional regulator, and EMF2 encodes a Polycomb group protein homolog. We examined expression profiles of emf mutants using GeneChip technology. The high degree of overlap in expression changes from the wild type among the emf1 and emf2 mutants was consistent with the functional similarity between the two genes. Expression profiles of emf seedlings before flower development were similar to that of Arabidopsis flowers, indicating the commitment of germinating emf seedlings to the reproductive fate. The germinating emf seedlings ectopically expressed flower organ genes, suggesting that vegetative development in wild-type plants results from EMF repression of the flower program, directly or indirectly. In addition, the seed development program is derepressed in the emf1 mutants. Gene expression analysis showed no clear regulation of CONSTANS (CO), FLOWERING LOCUS T (FT), LEAFY (LFY), and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 by EMF1. Consistent with epistasis results that co, lfy, or ft cannot rescue rosette development in emf mutants, these data show that the mechanism of EMF-mediated repression of flower organ genes is independent of these flowering genes. Based on these findings, a new mechanism of EMF-mediated floral repression is proposed.

Arabidopsis↗

[A study of lateral skull radiography of patients with submucous cleft palate].

OBJECTIVE: To investigate the insertion position of the levator veli palatini in the soft palate with SMCP comparing normal group and find out reliance diagnosis methods for SMCP. METHODS: Experimental group: lateral skull radiography film were taken in 50 patients with SMCP at rest and "i" phonation. Five parameters were measured which are relative length of soft palate and hard palate; levatorveli palatini insertion in the soft palate; elongation and angle of soft palate when lifting up on phonation. CONTROL GROUP: Ten sets (rest and pronouncing "i") of lateral skull radiography were used as control group. X-rays were taken for ten normal subjects without speech disorder or other abnormal physical situations. All data were subjected to the t-test of statistical significance. RESULTS: The difference of measures between patients with SMCP and normal control was significant (P <or= 0.05). CONCLUSION: It was obvious that both absolute and relative length of soft palate are short and levator muscle insert into soft palate arterially in patients with SMCP comparing with normal group, which caused VPI and become one of the criterias for SMCP.

Adolescent↗

[Clinical feature and airway inflammation in eosinophilic bronchitis].

OBJECTIVE: To study the clinical features and airway inflammation in eosinophilic bronchitis (EB) and the treatment outcomes. METHODS: Irwin's anatomic protocol for diagnosing chronic cough was used in 86 patients with chronic cough, and induced sputum by hypertonic saline aerosol inhalation was performed. Differential cell counts were performed in induced sputum, and eosinophilic cationic protein (ECP) was measured with fluoroimmunoassay, while interleukin-8 (IL-8) was measured with enzyme-linked absorbed immunoassay. EB was diagnosed according to Gibson's criteria and treated with inhaled budesonide 200 - 400 micro g twice daily for four weeks, and in some patients oral prednisone 10 - 15 mg/d or methyl-prednisone 8 - 12 mg/d was given for one week. RESULTS: 13 (15%) out of 86 patients with chronic cough were diagnosed as having EB. Dry cough was the major compliant and all had normal lung function with negative histamine provocation test. The Eos count was 0.1862 +/- 0.1632 and the concentration of ECP (2.53 +/- 2.07) mg/L in induced sputum were significant higher in patients with EB as compared with those normal subjects (P < 0.01). The cough disappeared in all patients at the end of one week of inhaled or orally administered corticosteroids. CONCLUSION: EB, an eosinophilic airway inflammation, is one of important causes of chronic cough and responds well to corticosteroid therapy.

Adolescent↗

Distinct regulation of salinity and genotoxic stress responses by Arabidopsis MAP kinase phosphatase 1.

The Arabidopsis genome contains 20 genes encoding mitogen-activated protein kinases (MAPKs), which drastically outnumbers genes for their negative regulators, MAP kinase phosphatases (MKPs) (five at most). This contrasts sharply with genomes of other eukaryotes where the number of MAPKs and MKPs is approximately equal. MKPs may therefore play an important role in signal integration in plants, through concerted regulation of several MAPKs. Our previous studies identified Arabidopsis MKP1 and showed that its deficiency in the mkp1 mutant results in plant hypersensitivity to genotoxic stress. Here, we identify a set of MAPKs that interact with MKP1, and show that the activity level of one of these, MPK6, is regulated by MKP1 in vivo. Moreover, using expression profiling, we identified a specific group of genes that probably represent targets of MKP1 regulation. Surprisingly, the identity of these genes and interacting MAPKs suggested involvement of MKP1 in salt stress responses. Indeed, mkp1 plants have increased resistance to salinity. Thus MKP1 apparently plays a pivotal role in the integration and fine-tuning of plant responses to various environmental challenges.

Arabidopsis↗

Analysis of differential gene expression by ligation specificity-based transcript profiling.

An open architecture mRNA profiling technology, LEAD (Ligation specificity-based Expression Analysis Display), was developed for studying differential gene expression. This method utilizes restriction enzymes with N(m) degeneracy in their recognition/cleavage sequences to fractionate cDNA population (N represents any one of the four possible bases; while m > or = 1, represents the number of degenerate bases). The fractionated cDNAs are subpooled by selective ligation with specific adapters, and then amplified and labeled by PCR. Fluorescent-labeled cDNA fingerprints are separated by electrophoresis as distinct bands with unique size and sequence, and quantified electronically by using the LEAD Finder program. The specificity of ligation and the uniform efficiency of PCR reaction allow precise quantification of differential gene expression among samples. Transcripts of low abundance (1/100,000 copies) can be detected, allowing the status of nearly all mRNA to be monitored. Because of its sequence independence, this technology can be used to monitor gene expression in both model and nonmodel systems lacking whole genome information. It can also be applied to separate and collect different cDNA species fingerprints to build a nonredundant EST library for microarray and other applications.

Animals↗

Transcriptional profiling reveals novel interactions between wounding, pathogen, abiotic stress, and hormonal responses in Arabidopsis.

Mechanical wounding not only damages plant tissues, but also provides pathways for pathogen invasion. To understand plant responses to wounding at a genomic level, we have surveyed the transcriptional response of 8,200 genes in Arabidopsis plants. Approximately 8% of these genes were altered by wounding at steady-state mRNA levels. Studies of expression patterns of these genes provide new information on the interactions between wounding and other signals, including pathogen attack, abiotic stress factors, and plant hormones. For example, a number of wound-responsive genes encode proteins involved in pathogen response. These include signaling molecules for the pathogen resistance pathway and enzymes required for cell wall modification and secondary metabolism. Many osmotic stress- and heat shock-regulated genes were highly responsive to wounding. Although a number of genes involved in ethylene, jasmonic acid, and abscisic acid pathways were activated, many in auxin responses were suppressed by wounding. These results further dissected the nature of mechanical wounding as a stress signal and identified new genes that may play a role in wounding and other signal transduction pathways.

Abscisic Acid↗

Transcriptome changes for Arabidopsis in response to salt, osmotic, and cold stress.

To identify genes of potential importance to cold, salt, and drought tolerance, global expression profiling was performed on Arabidopsis plants subjected to stress treatments of 4 degrees C, 100 mM NaCl, or 200 mM mannitol, respectively. RNA samples were collected separately from leaves and roots after 3- and 27-h stress treatments. Profiling was conducted with a GeneChip microarray with probe sets for approximately 8,100 genes. Combined results from all three stresses identified 2,409 genes with a greater than 2-fold change over control. This suggests that about 30% of the transcriptome is sensitive to regulation by common stress conditions. The majority of changes were stimulus specific. At the 3-h time point, less than 5% (118 genes) of the changes were observed as shared by all three stress responses. By 27 h, the number of shared responses was reduced more than 10-fold (< 0.5%), consistent with a progression toward more stimulus-specific responses. Roots and leaves displayed very different changes. For example, less than 14% of the cold-specific changes were shared between root and leaves at both 3 and 27 h. The gene with the largest induction under all three stress treatments was At5g52310 (LTI/COR78), with induction levels in roots greater than 250-fold for cold, 40-fold for mannitol, and 57-fold for NaCl. A stress response was observed for 306 (68%) of the known circadian controlled genes, supporting the hypothesis that an important function of the circadian clock is to "anticipate" predictable stresses such as cold nights. Although these results identify hundreds of potentially important transcriptome changes, the biochemical functions of many stress-regulated genes remain unknown.

Adaptation, Physiological↗