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Qing Ma

Publications and source records attributed to Qing Ma.

At least 19 recordsLinked to original sources
PubMed2025

Evolutionary Process Underlying Receptor Gene Expansion and Cellular Divergence of Olfactory Sensory Neurons in Honeybees.

Olfaction is crucial for animals' survival and adaptation. Unlike the strict singular expression of odorant receptor (OR) genes in vertebrate olfactory sensory neurons (OSNs), insects exhibit complex OR gene expression patterns. In honeybees (Apis mellifera), a significant expansion of OR genes implies a selection preference for the olfactory demands of social insects. However, the mechanisms underlying receptor expression specificity and their contribution to OSN divergence remain unclear. In this study, we used single-nucleus multiomics profiling to investigate the transcriptional regulation of OR genes and the cellular identity of OSNs in A. mellifera. We identified three distinct OR expression patterns, singular OR expression, co-expression of multiple OR genes with a single active promoter, and co-expression of multiple OR genes with multiple active promoters. Notably, ∼50% of OSNs co-expressed multiple OR genes, driven by polycistronic transcription of tandemly duplicated OR genes via a single active promoter. In these OSNs, their identity was determined by the first transcribed receptor. The divergent activation of the promoter for duplicated OR genes ensures the coordinated increased divergence of OSN population. By integrating multiomics data with genomic architecture, we illustrate how fundamental genetic mechanisms drive OR gene expansion and influence flanking regulatory elements, ultimately contributing to the cellular divergence of OSNs. Our findings highlight the interplay between gene duplication and regulatory evolution in shaping OSN diversity, providing new insights into the evolution and adaptation of olfaction in social insects. This study also sheds light on how genetic innovations contribute to the evolution of complex traits.

Animals↗
PubMed2006

Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure.

An important event in the pathogenesis of heart failure is the development of pathological cardiac hypertrophy. In cultured cardiomyocytes, the transcription factor Gata4 is required for agonist-induced hypertrophy. We hypothesized that, in the intact organism, Gata4 is an important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress. To test this hypothesis, we studied mice heterozygous for deletion of the second exon of Gata4 (G4D). At baseline, G4D mice had mild systolic and diastolic dysfunction associated with reduced heart weight and decreased cardiomyocyte number. After transverse aortic constriction (TAC), G4D mice developed overt heart failure and eccentric cardiac hypertrophy, associated with significantly increased fibrosis and cardiomyocyte apoptosis. Inhibition of apoptosis by overexpression of the insulin-like growth factor 1 receptor prevented TAC-induced heart failure in G4D mice. Unlike WT-TAC controls, G4D-TAC cardiomyocytes hypertrophied by increasing in length more than width. Gene expression profiling revealed up-regulation of genes associated with apoptosis and fibrosis, including members of the TGF-beta pathway. Our data demonstrate that Gata4 is essential for cardiac function in the postnatal heart. After pressure overload, Gata4 regulates the pattern of cardiomyocyte hypertrophy and protects the heart from load-induced failure.

Animals↗
PubMed2006

Development of heart valves requires Gata4 expression in endothelial-derived cells.

Cardiac malformations due to aberrant development of the atrioventricular (AV) valves are among the most common forms of congenital heart disease. At localized swellings of extracellular matrix known as the endocardial cushions, the endothelial lining of the heart undergoes an epithelial to mesenchymal transition (EMT) to form the mesenchymal progenitors of the AV valves. Further growth and differentiation of these mesenchymal precursors results in the formation of portions of the atrial and ventricular septae, and the generation of thin, pliable valves. Gata4, which encodes a zinc finger transcription factor, is expressed in the endothelium and mesenchyme of the AV valves. Using a Tie2-Cre transgene, we selectively inactivated Gata4 within endothelial-derived cells. Mutant endothelium failed to undergo EMT, resulting in hypocellular cushions. Mutant cushions had decreased levels of Erbb3, an EGF-family receptor essential for EMT in the atrioventricular cushions. In Gata4 mutant embryos, Erbb3 downregulation was associated with impaired activation of Erk, which is also required for EMT. Expression of a Gata4 mutant protein defective in interaction with Friend of Gata (FOG) cofactors rescued the EMT defect, but resulted in a decreased proliferation of mesenchyme and hypoplastic cushions that failed to septate the ventricular inlet. We demonstrate two novel functions of Gata4 in development of the AV valves. First, Gata4 functions as an upstream regulator of an Erbb3-Erk pathway necessary for EMT, and second, Gata4 acts to promote cushion mesenchyme growth and remodeling.

Animals↗
PubMed2006

Molecular weight dependent tissue factor pathway inhibitor release by heparin and heparin oligosaccharides.

Heparin and low molecular weight heparins exert their vascular effects by mobilizing tissue factor pathway inhibitor (TFPI) from the vascular endothelium into the blood circulation. We compared the influence of molecular weight on the TFPI release by heparin and its fractions in a non-human primate model. Primates were treated with unfractionated heparin, a low molecular weight heparin (gammaparin), or a heparin-derived oligosaccharide mixture (C3). Endothelial TFPI release was determined using both immunologic and functional assays. After intravenous administration, all agents significantly increased TFPI levels (p<0.05) in a dose dependent manner. The increase produced by unfractionated heparin and gammaparin was greater than that by C3 at an equal dosage (p<0.05). With subcutaneous injection, all agents produced less TFPI release. Repeated administration of heparin-derived oligosaccharides gradually increased TFPI release. A 1.89 fold increase in TFPI levels was observed 4 days after C3 treatment (2.5 mg/kg). Our findings indicated that TFPI release is dependent on the molecular weight of heparin and its derivatives. Heparin oligosaccharides exert their vascular effects through increased TFPI release after long-term repeated administration.

Animals↗
PubMed2006

Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease.

BACKGROUND: We previously showed that tumor-free peritoneum of patients with epithelial ovarian cancer (EOC) exhibited enhanced expression of several inflammatory response genes compared to peritoneum of benign disease. Here, we examined peritoneal inflammatory cell patterns to determine their concordance with selected enhanced genes. METHODS: Expression patterns of selected inflammatory genes were mined from our previously published data base. Bilateral pelvic peritoneal and subjacent stromal specimens were obtained from 20 women with EOC and 7 women with benign pelvic conditions. Sections were first stained by indirect immunoperoxidase and numbers of monocytes/macrophages (MO/MA), T cells, B cells, and NK cells counted. Proportions of CD68+ cells and CD3+ cells that coexpressed MO/MA differentiation factors (CD163, CCR1, CXCR8, VCAM1, and phosphorylated cytosolic phospholipase A2 [pcPLA2]), which had demonstrated expression in EOC peritoneal samples, were determined by multicolor immunofluorescence. RESULTS: MO/MA were present on both sides of the pelvic peritoneum in EOC patients, with infiltration of the subjacent stroma and mesothelium. CD68+ MO/MA, the most commonly represented population, and CD3+ T cells were present more often in EOC than in benign pelvic tumors. NK cells, B cells, and granulocytes were rare. CXCL8 (IL-8) and the chemokine receptor CCR1 were coexpressed more frequently on MO/MA than on CD3+ cells contrasting with CD68+/CD163+ cells that coexpressed CXCL8 less often. An important activated enzyme in the eicosanoid pathway, pcPLA2, was highly expressed on both CD68+ and CD163+ cells. The adherence molecule Vascular Cell Adhesion Molecule-1 (VCAM1) was expressed on CD31+ endothelial cells and on a proportion of CD68+ MO/MA but rarely on CD3+ cells. CONCLUSION: The pelvic peritoneum in EOC exhibits a general pattern of chronic inflammation, represented primarily by differentiated MO/MA, and distinct from that in benign conditions concordant with previous profiling results.

Journal Article↗
PubMed2006

Kidney NGAL is a novel early marker of acute injury following transplantation.

Acute kidney injury secondary to ischemia-reperfusion in renal allografts often results in delayed graft function. We tested the hypothesis that expression of neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of acute kidney injury following transplantation. Sections from paraffin-embedded protocol biopsy specimens obtained at approximately one hour of reperfusion after transplantation of 13 cadaveric (CAD) and 12 living-related (LRD) renal allografts were examined by immunohistochemistry for expression of NGAL. The staining intensity was correlated with cold ischemia time, peak post-operative serum creatinine, and dialysis requirement. There were no differences between the LRD and CAD groups in age, gender or preoperative serum creatinine. Using a scoring system of 0 (no staining) to 3 (most intense staining), NGAL expression was significantly increased in CAD specimens (2.3+/-0.8 versus 0.8+/-0.7 in LRD, p<0.001). There was a strong correlation between NGAL staining intensity and cold ischemia time (R=0.87, p<0.001). Importantly, NGAL staining in these early CAD biopsies was strongly correlated with peak postoperative serum creatinine, which occurred days later (R=0.86, p<0.001). Four patients developed delayed graft function requiring dialysis during the first week posttransplantation; all of these patients displayed the most intense NGAL staining in their first protocol biopsies. We conclude that NGAL staining intensity in early protocol biopsies represents a novel predictive biomarker of acute kidney injury following transplantation.

Acute Kidney Injury↗
PubMed2006

The structure of gelsolin bound to ATP.

Calcium activation of the actin-modifying properties of gelsolin is sensitive to ATP. Here, we show that soaking calcium-free gelsolin crystals in ATP-containing media results in ATP occupying a site that spans the two pseudosymmetrical halves of the protein. ATP binding involves numerous polar and hydrophobic contacts and is identical for the two copies of gelsolin related by non-crystallographic symmetry within the crystal. The gamma-phosphate of ATP participates in several charge-charge interactions consistent with the preference of gelsolin for ATP, as a binding partner, over ADP. In addition, disruption of the ATP-binding site through Ca2+ activation of gelsolin reveals why ATP binds more tightly to the inactive molecule, and suggests how the binding of ATP may modulate the sensitivity of gelsolin to calcium ions. Similarities between the ATP and PIP2 interactions with the C-terminal half of gelsolin are evident from their overlapping binding sites and in that both molecules bind more tightly in the absence of calcium ions. We propose a model for how PIP2 may bind to calcium-free gelsolin based on the ATP-binding site.

Adenosine Triphosphate↗
PubMed2006

Single and combination toxic metal exposures induce apoptosis in cultured murine podocytes exclusively via the extrinsic caspase 8 pathway.

Arsenite, cadmium, and mercury are among the most abundant toxic metals (TM) in the environment. Although the most common renal manifestation of TM toxicity is proximal tubular dysfunction, significant glomerular injury can also occur. We hypothesized that glomerular injury following TM exposure results from TM-induced apoptosis of podocytes. To test this hypothesis we examined the extent of apoptosis and the apoptotic pathways induced in cultured murine podocytes incubated for three days with arsenite, cadmium, or mercury, and with equimolar combinations of all three metals. Apoptosis was detected by DNA laddering, and the number of apoptotic nuclei determined by Tunel assay. Treatment for three days with each TM resulted in DNA laddering and induced a dose-dependent increase in apoptotic nuclei. In contrast, treatment with equimolar combinations of TM induced significantly fewer apoptotic nuclei than individual TM treatments. Apoptosis induced by each TM was associated with a significant (approximately 400%) increase in caspase 8 activity, but no change in caspase 9 activity, and Western analyses revealed a marked up-regulation of Fas (approximately 500%) and FADD (approximately 300%) with no change in expression of Bax, Bcl-2, or Bcl-xL. Similar to the apoptotic response, combinations of TM induced less caspase 8 activity and Fas/FADD expression than individual TM treatments. Collectively, these results demonstrate that (1) TM induced apoptosis in cultured murine podocytes via the extrinsic Fas-FADD caspase 8 pathway, rather than the mitochondrial apoptotic pathway, and (2) combination TM exposure induced less apoptosis than individual TM, indicating an antagonistic rather than an additive or synergistic toxicity.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Reduction in air bubble size using perfluorocarbons during cardiopulmonary bypass in the rat.

BACKGROUND: Perfluorocarbon (PFC) emulsions are artificial oxygen-carrying compounds with a high solubility for gases that have experimentally been shown to ameliorate cerebral air embolism. Cerebral air embolism has been associated with adverse cerebral outcomes after cardiac surgery using cardiopulmonary bypass (CPB). We designed this study to test whether PFC emulsions could reduce the volume of bubbles within the CPB circuit. METHODS: Male Sprague-Dawley rats undergoing 60 min of normothermic nonpulsatile CPB were randomized to one of the three groups. The PFC group (n = 10) received 60% O(2)/36% N(2)/4% CO(2) via the membrane oxygenator and 2.7 g/kg (4.5 mL/kg) of PFC into the venous reservoir; the control group (n = 10) received the same gas mixture and 4.5 mL/kg of saline; the N(2)O group (n = 6) was exposed to 36% N(2)O/60% O(2)/4% CO(2) and received 4.5 mL/kg of saline. After 10 min and 35 min of CPB, 400 microL of air was injected into a bubble chamber in the CPB circuit. After 20 min, the bubble was removed for volumetric analysis. RESULTS: Compared with baseline, the bubble decreased 13% +/- 5% in size in the PFC group and increased 46% +/- 9% in the nitrous oxide group, both of these changes significantly different from the control group (P < 0.0001). CONCLUSION: The results suggest that PFC administration may be useful in reducing the volume of gaseous bubbles present during CPB.

Animals↗
PubMed2006

[The experimental research for dielectric spectroscopy of human blood cells].

The dielectric spectroscopy of human blood cells was measured within the frequency range of 0.01-100 MHz, and the dielectric numerical characters were determined as response to AC electric field. we measured the AC impedance of normal human blood cells with the impedance technique in the frequency domain, then the experimental data were drawn a relationship curve between the frequency of electric field and conductivity. The dielectric spectrum and the Cole-Cole plots of human blood cells were established. The characteristics of dielectric response of human blood cells were also established. The permittivity and the conductivity of human blood cells were frequency dependent, and dielectric dispersion of human blood cells had two characteristic frequencies: i.e. fc1, is 1.42 MHz, and fc2 is 3. 32 MHz.

Blood Cells↗
PubMed2005

Morphogenesis of the right ventricle requires myocardial expression of Gata4.

Mutations in developmental regulatory genes have been found to be responsible for some cases of congenital heart defects. One such regulatory gene is Gata4, a zinc finger transcription factor. In order to circumvent the early embryonic lethality of Gata4-null embryos and to investigate the role of myocardial Gata4 expression in cardiac development, we used Cre/loxP technology to conditionally delete Gata4 in the myocardium of mice at an early and a late time point in cardiac morphogenesis. Early deletion of Gata4 by Nkx2-5Cre resulted in hearts with striking myocardial thinning, absence of mesenchymal cells within the endocardial cushions, and selective hypoplasia of the RV. RV hypoplasia was associated with downregulation of Hand2, a transcription factor previously shown to regulate formation of the RV. Cardiomyocyte proliferation was reduced, with a greater degree of reduction in the RV than in the LV. Late deletion of Gata4 by Cre recombinase driven by the alpha myosin heavy chain promoter did not selectively affect RV development or generation of endocardial cushion mesenchyme but did result in marked myocardial thinning with decreased cardiomyocyte proliferation, as well as double-outlet RV. Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal.

Animals↗
PubMed2005

Functional properties of PDIA from Aspergillus niger in renaturation of proteins.

Functional properties of protein disulfide isomerase A (PDIA) from Aspergillus niger were investigated using ribonuclease A, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and prochymosin as substrates. PDIA was shown to function as an isomerase catalyzing the refolding of denatured and reduced ribonuclease A. PDIA also exhibited trx-independent chaperone activity preventing the aggregation of reduced, denatured GAPDH, an enzyme lacking disulfide bonds. Both isomerase activity and chaperone function of PDIA were essential for the efficient refolding of the reduced, denatured prochymosin.

Aspergillus niger↗
PubMed2005

Pharmacokinetics and pharmacodynamics of enoxaparin in multiple trauma patients.

BACKGROUND: Enoxaparin is the only low molecular-weight heparin (LMWH) with documented efficacy for the prevention of venous thromboemobolism (VTE) following trauma, and it is currently considered the treatment of choice. Recent reports have suggested that the pharmacokinetics (PK) and pharmacodynamics of LMWH products may be altered in critically ill patients. METHODS: Two cohorts of critically ill multiple trauma patients were enrolled in this study: A (nonedematous) and B (edematous, defined as the presence of peripheral edema and an increase in body weight of > or =10 kg). All patients received at least four doses of enoxaparin 30 mg subcutaneously every 12 hours before the study dose. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours following a morning dose. Plasma anti-Xa and antithrombin (AT) activities were determined using chromogenic assays. A compartmental PK analysis model was defined for the data. PK parameters for the two cohorts were compared using a Mann-Whitney Rank Sum test. RESULTS: The area under the curve (AUC)0-12 hour, maximal plasma anti-activated Factor Xa (anti-Xa) activity (Amax), and AT activity were significantly lower in the edematous trauma patients (p < 0.05). The AUC0-12 hour for plasma anti-Xa activity was highly variable in both study cohorts. Seven of the 10 edematous patients had barely quantifiable anti-Xa results. Activity levels were too low to reliably estimate the PK parameters for most patients in cohort B. CONCLUSION: The standard dose of enoxaparin recommended for the prevention of VTE following multiple trauma provides unreliable and highly variable anti-Xa activity in critically ill trauma patients, and is strongly affected by the presence of significant peripheral edema.

Adult↗
PubMed2005

Induction of Zf9 in the kidney following early ischemia/reperfusion.

BACKGROUND: An improved understanding of the early cell injury mechanisms is critical for effective therapy of acute renal failure (ARF). METHODS: We utilized cDNA microarrays to identify renal genes that are induced very early after renal ischemia in a mouse model, whose protein products might provide novel information regarding the pathogenesis of ARF. The findings were confirmed by downstream mRNA and protein expression studies, as well as knockdown analysis with antisense primers. RESULTS: The maximally induced gene (21-fold at 3 hours of reflow) was Zf9, a Kruppel-like transcription factor involved in the regulation of transforming growth factor-beta1 (TGF-beta1). The rapid induction of Zf9 mRNA was confirmed by Northern analysis (14.5-fold at 3 hours of reflow) and that of Zf9 protein by Western analysis (10.5-fold at 3 hours of reflow). Zf9 protein was induced in both proximal and distal tubule cells in a cytoplasmic as well as nuclear distribution. TGF-beta1 protein was also up-regulated in a pattern parallel to that of Zf9. In cultured human proximal tubule cells, induction of ischemia by partial adenosine triphosphate (ATP) depletion resulted in a rapid up-regulation of both Zf9 and of TGF-beta1 proteins. Antisense oligonucleotides to Zf9 markedly blunted the induction of Zf9 and TGF-beta1, and significantly inhibited the apoptotic response to ATP depletion. CONCLUSION: Induction of Zf9 and its transactivating factor TGF-beta1 may play a critical and hitherto unrecognized role in the early apoptotic response to ischemic renal injury.

Acute Kidney Injury↗
PubMed2005

Functional analysis of tunicamycin-inducible gene A polypeptide from Aspergillus niger.

Tunicamycin-inducible gene A polypeptide (TIGA) is a member of the protein disulfide isomerase (PDI) family and is suggested to facilitate the folding of nascent polypeptides. The functional properties of TIGA were investigated here. TIGA acted as an isomerase, catalyzing the refolding of denatured and reduced ribonuclease A. TIGA also exhibited chaperone activity in the refolding of denatured prochymosin but not in the refolding of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), indicating that it had substrate specificity with respect to chaperone activity. Detailed study with a series of thioredoxin-motif (trx-motif) mutants revealed that the 2 trx-motifs of TIGA were not equal in activity. The N-terminal trx-motif was more active than the C-terminal trx-motif, and the first cysteine in each trx-motif was necessary for isomerase activity.

Aspergillus niger↗
PubMed2005

The histone deacetylase inhibitor butyrate downregulates cyclin B1 gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells.

Histone deacetylase (HDAC) inhibitors are showing promise as treatment for a variety of human cancers, but their precise mechanism of action has not been elucidated. We examined the effects of the HDAC inhibitor butyrate on colon cancer cells, focusing on its effect on the cell cycle promoter cyclin B(1). In HT-29 cells, sodium butyrate-mediated growth inhibition is associated with a marked decrease in cyclin B(1) mRNA levels. The decrease in cyclin B(1) occurred in a delayed fashion (at 24 h), is completely blocked by concomitant treatment with protein synthesis inhibitors, and appears to be dependent on changes in transcription. Cyclin B(1) repression is linked to the differentiation process in colon cancer cells, not merely with growth arrest. The mechanism of cyclin B(1) repression by butyrate requires prolonged histone hyperacetylation and is at least partly dependent on p21 expression. In fact, p21/WAF-1 appears to directly repress a minimal cyclin B(1) promoter (-90 bp), a process that can be mediated by the amino-terminal portion of the p21 protein. These findings highlight key molecular mechanisms by which HDAC inhibitors mediate their beneficial effects on human cancer cells.

Acetylation↗
PubMed2005

Pharmacokinetic drug interactions with non-nucleoside reverse transcriptase inhibitors.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a diverse group of compounds that inhibit HIV Type 1 reverse transcriptase. Although possessing a common mechanism of action, the approved NNRTIs, delavirdine, efavirenz and nevirapine, differ in structural and pharmacokinetic characteristics. Each of the NNRTIs undergoes biotransformation by the cytochrome P450 (CYP) enzyme system, thus making them prone to clinically significant drug interactions when combined with other antiretrovirals. In addition, they interact with other concurrent medications and complementary/alternative medicines, acting as either inducers or inhibitors of drug-metabolising CYP enzymes. These drug interactions become an important consideration in the clinical use of these agents when designing combination regimens, as recommended by current guidelines. This review provides an updated summary of pharmacokinetic interactions with NNRTIs.

Animals↗