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Biomedical subjects

Ping Wu

Publications and source records attributed to Ping Wu.

At least 37 records · Page 2Linked to original sources

OsEIL1, a rice homolog of the Arabidopsis EIN3 regulates the ethylene response as a positive component.

The plant gaseous hormone ethylene regulates many aspects of plant growth, development and responses to the environment. ETHYLENE INSENSITIVE3 (EIN3) is a transcription factor involved in the ethylene signal transduction pathway in Arabidopsis. To gain a better understanding of the ethylene signal transduction pathway in rice, six EIN3-like genes (designated OsEIL1-6) were identified. OsEIL1, which showed highest similarity with EIN3, was isolated and functionally characterized. Ectopic expression of OsEIL1 in Arabidopsis can partially complement the ein3-1 mutant. The transgenic rice plants with overexpression of OsEIL1 exhibit short root, coiled primary root and slightly short shoot phenotype and elevated response to exogenous ethylene. OsEBP89, an ethylene responsive element binding protein (EREBP) and OsACO1, an ACC (1-aminocyclopropane-1-carboxylic acid) oxidase gene were enhanced in the OsEIL1 overexpressing transgenic plants. These results indicate that OsEIL1 is involved in ethylene signal transduction pathway and acts as a positive regulator of ethylene response in rice.

Amino Acid Oxidoreductases↗

The crystal structure of murine coronin-1: a regulator of actin cytoskeletal dynamics in lymphocytes.

Mammalian coronin-1 is preferentially expressed in hematopoietic cells and plays a poorly understood role in the dynamic reorganization of the actin cytoskeleton. Sequence analysis of coronin-1 revealed five WD40 repeats that were predicted to form a beta propeller. They are followed by a 130 residue extension and a 30 residue leucine zipper domain that is responsible for multimerization of the protein. Here, we present the crystal structure of murine coronin-1 without the leucine zipper at 1.75 A resolution. Coronin-1 forms a seven-bladed beta propeller composed of the five predicted WD40 repeats and two additional blades that lack any homology to the canonical WD40 motif. The C-terminal extension adopts an extended conformation, packs tightly against the bottom surface of the propeller, and is likely to be required for the structural stability of the propeller. Analysis of charged and conserved surface residues delineate possible binding sites for F-actin on the beta propeller.

Actins↗

Engineering stem cells into organs: topobiological transformations demonstrated by beak, feather, and other ectodermal organ morphogenesis.

To accomplish regenerative medicine, several critical issues in stem cell biology have to be solved, including the identification of sources, the expanding population, building them into organs, and assimilating them to the host. Although many stem cells can now differentiate along certain lineages, knowledge on how to use them to build organs lags behind. Here we focus on topobiological events that bridge this gap, for example, the regulation of number, size, axes, shape, arrangement, and architecture during organogenesis. Rather than reviewing detail molecular pathways known to disrupt organogenesis when perturbed, we highlight conceptual questions at the topobiological level and ask how cellular and molecular mechanisms can work to explain these phenomena. The avian integument is used as the Rosetta stone because the molecular activities are linked to organ forms that are visually apparent and have functional consequences during evolution with fossil records and extant diversity. For example, we show that feather pattern formation is the equilibrium of stochastic interactions among multiple activators and inhibitors. Although morphogens and receptors are coded by the genome, the result is based on the summed physical-chemical properties on the whole cell's surface and is self-organizing. For another example, we show that developing chicken and duck beaks contain differently configured localized growth zones (LoGZs) and can modulate chicken beaks to phenocopy diverse avian beaks in nature by altering the position, number, size, and duration of LoGZs. Different organs have their unique topology and we also discuss shaping mechanisms of liver and different ways of branching morphogenesis. Multi-primordium organs (e.g., feathers, hairs, and teeth) have additional topographic specificities across the body surface, an appendage field, or within an appendage. Promises and problems in reconstitute feather/hair follicles and other organs are discussed. Finally, simple modification at the topobiological level may lead to novel morphology for natural selection at the evolution level.

Animals↗

QTLs and candidate genes for rice root growth under flooding and upland conditions.

To investigate the genetic factors underlying constitutive and adaptive root growth under different water-supply conditions, a double haploid (DH) population, derived from a cross between lowland rice variety IR64 and upland rice variety Azucena, with 284 molecular markers was used in cylindrical pot experiments. Several QTLs for seminal root length (SRL), adventitious root number (ARN) and total root dry weight (RW) respectively, under both flooding and upland conditions were detected. Two identical QTLs for SRL and RW were found under flooding and upland conditions. The relative parameters defined as the ratio of parameters under the two water-supply conditions were also used for QTL analysis. A comparative analysis among different genetic populations was performed for the QTLs for root traits and several consistent QTLs for root traits across genetic backgrounds were detected. Candidate genes for cell expansion and elongation were used for comparative mapping with the detected QTLs. Four cell wall-related expressed sequence tags (ESTs) for OsEXP2, OsEXP4, EXT and Xet were mapped on the intervals carrying the QTLs for root traits.

Adaptation, Physiological↗

Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors.

BACKGROUND: Enrolling participants onto clinical trials of cancer presents an important challenge. We aimed to identify the concerns of patients with cancer about, and the barriers to, participation in clinical trials. METHODS: We did a systematic review to assess studies of barriers to participation in experimental trials and randomised trials for validity and content. We estimated the frequency with which patients identified particular issues by pooling across studies that presented data for barriers to participation in clinical trials as proportions. FINDINGS: We analysed 12 qualitative studies (n=722) and 21 quantitative studies (n=5452). Two qualitative studies inquired of patients who were currently enrolled onto clinical trials, and ten inquired of patients who were eligible for enrolment onto various clinical trials. Barriers to participation in clinical trials were protocol-related, patient-related, or physician-related. The most common reasons cited as barriers included: concerns with the trial setting; a dislike of randomisation; general discomfort with the research process; complexity and stringency of the protocol; presence of a placebo or no-treatment group; potential side-effects; being unaware of trial opportunities; the idea that clinical trials are not appropriate for serious diseases; fear that trial involvement would have a negative effect on the relationship with their physician; and their physician's attitudes towards the trial. Meta-analysis confirmed the findings of our systematic review. INTERPRETATION: The identification of such barriers to the participation in clinical trials should help trialists to develop strategies that will keep to a maximum participation and cooperation in cancer trials, while informing and protecting prospective participants adequately.

Clinical Trials as Topic↗

Barriers to participation in HIV drug trials: a systematic review.

The enrolling of adequate participants into HIV experimental drug trials presents an important challenge. We systematically reviewed the literature to identify barriers and concerns amongst HIV patients to participation in HIV clinical drug trials. We reviewed studies for validity and content, and generated pooled estimates of the frequency with which patients identified particular issues by pooling across studies that presented results as proportions. We included three semi-structured interview studies, two open-ended questionnaires, and nine quantitative studies. Major barriers to participation included fear of side-effects, distrust of researchers, general concerns about research design, interference in everyday life or changes in routine, and social discrimination. Results from the quantitative studies indicated that the most prevalent barriers were as follows: suspicions about the drug itself (53%, 95% CI 24-83%), patients were not informed or believed they were not eligible (38%, 25-50%), and travel or transport obstacles (39%, 21-57%). The findings of this study should aid drug trialists in developing strategies to maximise participation and cooperation in HIV clinical drug trials while adequately informing and protecting prospective participants.

Anti-HIV Agents↗

The combination of cyclophosphomide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide - vincristine - doxorubicin - methylprednisolone as induction chemotherapy prior to autologous transplantation for multiple myeloma: a case-matched analysis.

A retrospective case-matched study was conducted to compare the oral regimen CTD (cyclophosphamide - thalidomide - dexamethasone) and infusional CVAMP (cyclophosphamide - vincristine - doxorubicin - methylprednisolone) as induction therapy followed by autologous peripheral blood stem-cell transplantation (PBSCT) for newly diagnosed multiple myeloma patients. The response rate after three cycles of treatment was statistically higher with CTD (n = 27) compared to CVAMP (n = 27) (89% vs. 56%, P = 0.016). Toxicity studies showed more neutropenia (grade 3/4) (4% vs. 60%, P = 0.0002) with CVAMP and more thrombotic episodes with CTD (11% vs. 4%). CTD may emerge as the superior induction regimen prior to PBSCT, in terms of high efficacy and better tolerability.

Adult↗

Mechanisms of microbially enhanced Fe acquisition in red clover (Trifolium pratense L.).

Soil microorganisms may play an important role in plant Fe uptake from soils with low Fe bioavailability, but there is little direct experimental evidence to date. We grew red clover, an Fe-efficient leguminous plant, in a calcareous soil to investigate the role of soil microbial activity in plant Fe uptake. Compared with plants grown in non-sterlie (NS) grown plants, growth and Fe content of the sterile(s) grown plants was significantly inhibited, but was improved by foliar application of Fe EDTA, indicating that soil microbial activity should play an important role in plant Fe acquisition. When soil solution was incubated with phenolic root exudates from Fe-deficient red clover, a few microbial species thrived while growth of the rest was inhibited, suggesting that the Fe-deficient (-Fe) root exudates selectively influenced the rhizosphere's microbial community. Eighty six per cent of the phenolic-tolerant microbes could produce siderophore [the Fe(III) chelator] under -Fe conditions, and 71% could secrete auxin-like compounds. Interestingly, the synthetic and microbial auxins (MAs) significantly enhanced the Ferric reduction system, suggesting that MAs, in addition to siderophores, are important to plant Fe uptake. Finally, plant growth and Fe uptake in sterilized soil were significantly increased by rhizobia inoculation. Root Fe-EDTA reductase activity in the -Fe plant was significantly enhanced by rhizobia infection, and the rhizobia could produce auxin but not siderophore under Fe-limiting conditions, suggesting that the contribution of nodulating rhizobia to plant Fe uptake can be at least partially attributed to stimulation of turbo reductase activity through nodule formation and auxin production in the rhizosphere. Based on these observations, we propose as a model that root exudates from -Fe plants selectively influence the rhizosphere microbial community, and the microbes in turn favour plant Fe acquisition by producing siderophores and auxins.

Indoleacetic Acids↗

Cytokinin represses phosphate-starvation response through increasing of intracellular phosphate level.

The involvement of cytokinins (CTKs) in the repression of phosphate (Pi)-starvation signalling has been widely documented. However, the full physiological and molecular relevance of this role remains unclear. To gain further insights into the regulation system of CTK repression of Pi-starvation signalling, a global analysis of gene expression events in rice seedlings under Pi starvation, and the exogenous CTK treatment under Pi-sufficient (+P) and Pi-deficient (-P) conditions, was conducted using oligonucleotide array analysis. Physiological and biochemical adaptation was observed after 10 d Pi starvation in rice seedlings. A global reduction of the Pi-starvation signalling was detected after 3 d treatment of exogenous CTK. Expression profiling data indicate that, together with a significant increase of intracellular Pi content, many expression changes responsive to Pi starvation were reversed by exogenous CTK treatment while CTK-responsive genes behaved normally under -P condition. These results suggest that the interplay of CTK signal and Pi-starvation response can be partially explained by the rise of Pi concentration after exogenous CTK treatment. Microarray data also revealed that a small number of genes have different CTK response patterns under different Pi levels, suggesting a subtle interaction between CTK and Pi-starvation signalling pathway.

Cytokinins↗

Sodium barbital is a slow reversible inactivator of rabbit-muscle creatine kinase.

As a depressant of the central nervous system, the clinical effect of sodium barbital has been extensively studied. Here we report on sodium barbital as an inhibitor of rabbit-muscle creatine kinase (CK), which plays a significant role in energy homeostasis in the muscles. Although sodium barbital gradually inhibits the activity of CK with increased concentration, the inhibition effect can be completely reversed by dilution, indicating that the inactivation process is reversible. Detailed kinetics analysis, according to a previously presented theory, indicates that sodium barbital functions as a non complexing inhibitor, and its inhibition effect on CK is a slow reversible inactivation. In this study, a kinetic model of the substrate reaction is presented, and the microscopic rate constants for the reaction of sodium barbital with the free enzyme and the enzyme-substrate complexes are determined. Kinetic analysis reveals that sodium barbital might compete with both creatine and ATP, but mainly with creatine, to inhibit the activity of CK. The results suggest that CK might be a target for sodium barbital in vivo.

Adenosine Triphosphate↗

Adherence to HAART: a systematic review of developed and developing nation patient-reported barriers and facilitators.

BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) medication is the greatest patient-enabled predictor of treatment success and mortality for those who have access to drugs. We systematically reviewed the literature to determine patient-reported barriers and facilitators to adhering to antiretroviral therapy. METHODS AND FINDINGS: We examined both developed and developing nations. We searched the following databases: AMED (inception to June 2005), Campbell Collaboration (inception to June 2005), CinAhl (inception to June 2005), Cochrane Library (inception to June 2005), Embase (inception to June 2005), ERIC (inception to June 2005), MedLine (inception to June 2005), and NHS EED (inception to June 2005). We retrieved studies conducted in both developed and developing nation settings that examined barriers and facilitators addressing adherence. Both qualitative and quantitative studies were included. We independently, in duplicate, extracted data reported in qualitative studies addressing adherence. We then examined all quantitative studies addressing barriers and facilitators noted from the qualitative studies. In order to place the findings of the qualitative studies in a generalizable context, we meta-analyzed the surveys to determine a best estimate of the overall prevalence of issues. We included 37 qualitative studies and 47 studies using a quantitative methodology (surveys). Seventy-two studies (35 qualitative) were conducted in developed nations, while the remaining 12 (two qualitative) were conducted in developing nations. Important barriers reported in both economic settings included fear of disclosure, concomitant substance abuse, forgetfulness, suspicions of treatment, regimens that are too complicated, number of pills required, decreased quality of life, work and family responsibilities, falling asleep, and access to medication. Important facilitators reported by patients in developed nation settings included having a sense of self-worth, seeing positive effects of antiretrovirals, accepting their seropositivity, understanding the need for strict adherence, making use of reminder tools, and having a simple regimen. Among 37 separate meta-analyses examining the generalizability of these findings, we found large heterogeneity. CONCLUSIONS: We found that important barriers to adherence are consistent across multiple settings and countries. Research is urgently needed to determine patient-important factors for adherence in developing world settings. Clinicians should use this information to engage in open discussion with patients to promote adherence and identify barriers and facilitators within their own populations.

Antiretroviral Therapy, Highly Active↗

A sensitive proximity ligation assay for active PSA.

Prostate-specific antigen (PSA) is a widely used marker for prostate cancer. The utility of PSA tests is limited by their inability to differentiate prostate cancer from non-malignant conditions such as benign prostatic hyperplasia and prostatitis. In circulation, PSA occurs in various complexed and free forms, and specific determination of some of these can be used to improve the diagnostic accuracy of PSA tests. We have previously identified peptides that specifically bind to enzymatically active PSA and using such a peptide we have developed an immunopeptidometric assay for this form of PSA. However, the sensitivity of that assay is too low to measure active PSA at clinically important levels. Recently a novel sensitive immunoassay for analysis of proteins, termed the proximity ligation assay, has been established. Here we describe a sensitive implementation of the proximity ligation assay, which utilizes a PSA-binding peptide and antibody as probes to detect active PSA. The assay has a sensitivity of 0.07 microg/l, which is approximately ten-fold lower than that of our previous assay. It does not cross-react with inactive proPSA or the highly similar kallikrein hK2. Our results show that a highly sensitive immunopeptidometric assay can be developed using proximity ligation. This principle should facilitate establishment of specific assays for active forms of other proteases.

Antibody Specificity↗

Childhood depressive symptoms and early onset of alcohol use.

OBJECTIVES: Few studies have assessed the relationship between depressive symptoms and early onset of alcohol use in children and early adolescents. We aimed to determine whether depressive symptoms in children are associated with subsequent initiation of alcohol use and, if so, whether this association is merely a result of demographic, parental, and/or individual risk factors shared by depression and alcohol use or independent of these shared risk factors. METHODS: Analyses were based on a subsample of 10- to 13-year-old children (N = 1119) from the Boricua Youth Study, a longitudinal study of psychopathology among Puerto Rican children and early adolescents. Children in the study were assessed over 3 waves between 2000 and 2004. In-person structured interviews were conducted with both parents and children. RESULTS: Depressive symptoms and alcohol use shared some significant risk and protective factors, such as parental psychopathology, parenting, child exposure to violence, and antisocial behaviors. After controlling for these factors, the association between depressive symptoms and alcohol use was reduced, but childhood depressive symptoms were still positively associated with subsequent alcohol use initiation. Children with medium or high levels of depressive symptoms were more than twice as likely to use alcohol as those with <2 depressive symptoms. CONCLUSIONS: The finding of the current study that early life depressive symptoms may lead to earlier onset of alcohol use indicates the importance of identifying and treating depressive symptoms in preadolescent children. It also demonstrates the importance of examining shared risk and protective factors for understanding the relationship between depressive symptoms and alcohol use.

Adolescent↗

[A preliminary analysis of the function of the OsRab5a gene in rice (Oryza sativa L.)].

OsRab5a encodes a Rab5 protein in rice, which belongs to the Rab family of small GTP-binding protein superfamily. Transgenic plants with POsrab5a::beta-glucuronidase (GUS) gene indicate that OsRab5a is expressed in callus, root, stem, leaf, root base and spikelet (Figs.1, 2H-1). Using the transgenic Arabidopsis with fused gene of GFP::OsRab5a and GFP::OsRab5aCA and by using FM4-64 (the lipophilic styryl dye) staining, we have demonstrated that OsRab5a is involved in vesicular transport and GFP-OsRab5a is localized on the plasma membrane and early endosomes (Fig.2A-C), while GFP-OsRab5aCA is localized in the cell membrane (Fig.2D-F). The reduction of expression of OsRab5a in callus RNA interference, however, led to the lethality of callus during differentiation (Fig.3D-F). The expression of OsRab5a was upregulated slightly by exogenous cytokinin (Fig.4), and was higher in the differentiation medium than that in selection medium (Fig.3G-I). These results suggest that OsRab5a plays an important role in callus differentiation probably through mediating hormone signal transduction.

Biological Transport↗

[Change of myocardial enzymes in patients with acute tetramine poisoning].

OBJECTIVE: To investigate the clinical significance of myocardial enzymes in patients with acute tetramine (TEM) poisoning. METHODS: The dynamic changes of the activity of myocardial enzymes and ECG were observed in 67 patients with acute TEM poisoning as well as in 67 healthy people for medical checkup at outpatient department as the control group. RESULTS: Myocardial enzymes of the patients with acute TEM poisoning were increased to different extents on the first day. There was significant difference in the activity of aspartate aminotransferase (AST), creatine phosphokinase (CPK), lactic dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) and CPK isoenzyme MB (CK-MB) between the patients and the healthy people in the control group (P < 0.01). There was significant difference in the myocardial enzymes at different time points among the patients with mild, middle and severe poisoning (P < 0.01). The severer the TEM poisoning was, the higher the activity of myocardial enzymes and the abnormal rate of ECG were. The activity of CPK was the earliest to rise with the highest aptitude of fluctuation and the longest time of elevation. The change of the myocardial enzymes was earlier than that of ECG. The abnormal rate of AST, CPK, CK-MB, LDH, alpha-HBDH was 86.57%, 98.51%, 94.03%, 89.55% and 79.10% respectively. The abnormal rate of ECG was 49.3% on the third day of poisoning. Measurement of myocardial enzymes was better than ECG in sensitivity. CONCLUSION: Acute tetramine poisoning can damage myocardium, which is reversible. CPK is a typical marker for the damage and can serve as one of the important clinical monitoring indices.

Acute Disease↗