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Biomedical subjects

Xuemin Wang

Publications and source records attributed to Xuemin Wang.

At least 19 recordsLinked to original sources
PubMed2026

Estimation Model of Pig Weight Based on Body Measurements and Analysis of Its Genetic Basis.

Body weight and body measurements are key indicators of growth and economic efficiency in pigs, but conventional weighing is labor-intensive and stressful, increasing disease risk and necessitating non-contact estimation. We measured five dimensions (body length, chest circumference, abdominal circumference, body width, and body height) in 811 Suzi black pigs and constructed six multiple linear regression models using different combinations. All models had R2&#x2009;>&#x2009;0.91, with adjusted R2 also exceeding 0.91, and the model combining length, chest, and abdominal circumference gave the lowest RMSE, balancing accuracy and practicality. Separately, we performed GWAS on 165 genotyped individuals (100&#x2009;K SNP chip and GBS) for age (as a growth rate proxy), body weight, and the five measurements. No SNP reached genome-wide significance (p&#x2009;<&#x2009;1.86&#x2009;&#xd7;&#x2009;10-6), but three suggestive loci (p&#x2009;<&#x2009;1.39&#x2009;&#xd7;&#x2009;10-5) were detected: SNP 4_12&#x2009;319&#x2009;200 for age (35.55% variance), a pleiotropic SNP 1_60&#x2009;912&#x2009;826 associated with length, chest, and abdominal circumference (42.10%, 53.06%, and 45.97% variance), and SNP 1_60&#x2009;638&#x2009;159 for abdominal circumference. Positional mapping identified EPHA7 as the nearest candidate gene. Enrichment analyses revealed focal adhesion, receptor tyrosine kinase, IgSF-CAM, integrin, and PI3K-Akt pathways, with EPHA7 and FYN as key regulators. Notably, the three traits in the best model mapped to the same pleiotropic locus, suggesting a shared genetic basis. This study provides a practical estimation tool and suggestive markers, supporting non-contact weighing systems and molecular breeding.

Animals↗
PubMed2025

A Swedish genome-wide haplotype association analysis identifies novel candidate loci associated with endometrial cancer risk.

Genome-wide association studies [GWAS] have identified a limited number of endometrial cancer risk loci by analyzing single nucleotide polymorphisms [SNPs]. We hypothesized that analyzing haplotypes rather than SNPs could provide novel and more detailed information on genetic cancer susceptibility loci. To examine the association of a SNP or haplotype with endometrial cancer risk we performed a two-stage haplotype GWAS. The discovery GWAS included a sub-cohort of 1,116 Swedish endometrial cancer cases and 5,021 controls from previously published GWAS data. A sliding window analysis was employed with window sizes of 1-25 SNPs using a logistic regression model. The Swedish haplotype analysis identified 15 novel candidate risk loci (2q31.1, 4p16.1, 4p15.31,&#xa0;6q13, 7p21.1, 9p13.3, 10q26.3, 11q21, 12q13.11, 13q12.11, 15q13.3, 16q24.3, 19q13.32, 20p12.3 and 22q13.2) with OR ranging from 1.6 to 3.3 and p-values from 4.25&#x2009;&#xd7;&#x2009;10-8 to 9.86&#x2009;&#xd7;&#x2009;10-15. A second replication haplotype analysis of the Swedish novel loci was performed using two cohorts from Belgium and Germany. In spite of small sample sizes in the replication cohorts, there was still support for most loci with positive ORs. In addition, the findings in the two European cohorts motivates further studies to search for founder haplotypes. These novel findings suggested that endometrial cancer loci, identified through haplotype analysis, conferred a higher risk compared to previous single-variant GWAS.

Humans↗
PubMed2006

Expression and characterization of Arabidopsis phospholipase Dgamma2.

The phospholipase D (PLD) family of Arabidopsis thaliana has 12 identified members, including three highly homologous PLDgammas. The enzymatic and molecular properties of PLDgamma2 were characterized and compared with those of PLDgamma1. Two variants of PLDgamma2 cDNAs, designated PLDgamma2a and PLDgamma2b, were isolated, and they differ in the presence of a 96-nucleotide fragment at the beginning of the open reading frame. Catalytically active PLDgamma2a was expressed in E. coli. PLDgamma2a and gamma1 both require phosphatidylinositol 4,5-bisphosphate (PIP(2)) and calcium for activity, but they differ in the effect of PIP(2) and Triton X-100 on their activities. While Triton X-100 could greatly activate PLDgamma1 activity and served only as a neutral diluent in the substrate vesicles, it totally abolished PLDgamma2a activity and prohibited any stimulation effect from PIP(2.) PLDgamma2a misses one of the basic, PIP(2)-interacting residues, which may weaken the binding of PIP(2) to PLDgamma2a. In addition, PLDgamma2 and PLDgamma1 displayed different patterns of expression in different tissues, and the transcript of PLDgamma2a differs from that of PLDgamma1 by having a longer 5'-UTR. These differences in biochemical and molecular properties suggest that the highly homologous PLDgammas are subjected to unique regulations and might have distinguishable functions.

Amino Acid Sequence↗
PubMed2006

Rapid characterization of the fatty acyl composition of complex lipids by collision-induced dissociation time-of-flight mass spectrometry.

Profiling of leaf extracts from mutants of Arabidopsis with defects in lipid desaturation demonstrates the utility of collision-induced dissociation time-of-flight mass spectrometry (CID-TOF MS) for screening biological samples for fatty acid compositional alterations. CID-TOF MS uses the collision cell of a quadrupole time-of-flight mass spectrometer to simultaneously fragment all of the ions produced by an ionization source. Electrospray ionization CID-TOF MS in the negative mode can be used to analyze fatty acyl anions derived from complex lipids as well as free fatty acids. Although acyl anion yield is shown to be a function of the lipid class and the position on the glycerol backbone, acyl compositional profiles can be determined, and the TOF detector provides resolution of nominally isobaric acyl species in the profiles. Good precision is obtained when data are acquired for approximately 1 min per sample.

Arabidopsis↗
PubMed2006

Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and Mammalian cells.

Resveratrol is a naturally occurring defense compound produced by a limited number of plants in response to stresses. Besides cardiovascular benefits, this health-promoting compound has been reported to extend life spans in yeasts, flies, worms, and fish. To biosynthesize resveratrol de novo, tyrosine ammonia lyase (TAL), 4-coumarate CoA-ligase (4CL), and stilbene synthase (STS) were isolated from Rhodobacter sphaeroides, Arabidopsis thaliana, and Vitis vinifera, respectively. Yeast cells expressing 4CL and STS produce resveratrol when fed with 4-coumaric acid, the substrate of 4CL. When a translational fusion protein joining 4CL and STS was used, yeast cells produced 15-fold more resveratrol than the cotransformed cells, suggesting that physical localization of 4CL and STS facilitate resveratrol production. When the resveratrol pathway was introduced into human HEK293 cells, de novo biosynthesis was detected, leading to intracellular accumulation of resveratrol. We successfully engineered an entire plant natural product pathway into a mammalian host.

Acyltransferases↗
PubMed2006

Evaluation of the superiority of insulin glargine as basal insulin replacement by continuous glucose monitoring system.

To evaluate the superiority of insulin glargine as basal insulin replacement by continuous glucose monitoring system (CGMS). Twenty-four patients with type 2 diabetes mellitus (T2DM) whose blood glucose was not well controlled with sulphanylureas were enrolled. At first, they were treated with extended-release glipizide (glucotrol XL) 5mg/d before breakfast for 2 weeks, then randomized to combination treatment with glargine (16 patients) or NPH (8 patients) and treated for 12 weeks. CGMS were carried in the second week after treatment with glucotrol XL, and in the 12th week after combination treatment. The data of CGMS showed: (1) When FPG were well controlled in both groups (glargine group versus NPH group: 6.0+/-1.0 mmol/L versus 5.8+/-1.3 mmol/L), the blood glucose level at 3:00 a.m. (5.1+/-0.9 mmol/L versus 4.2+/-0.8 mmol/L) were higher (P<0.05), TPG< or =3.0 mmol/L at night were lower (2.56+/-1.79 versus 5.88+/-1.96), and the rate of nocturnal hypoglycemia (1/16 versus 4/8) were less (P=0.028) in glargine group than those in NPH group. (2) CGMS showed that the daily blood glucose profile excursion were more smoother in glargine group than those in NPH group. In conclusion, it was confirmed with CGMS that compared with traditionally basal insulin replacement with NPH, the combination treatment with glargine injection at bedtime may be predominant for stabilizing the daily blood glucose profile excursion and decreasing the nocturnal hypoglycemia events incidence. So glargine may be a more ideal basal insulin replacement than NPH.

Blood Glucose↗
PubMed2006

Quantitative profiling of Arabidopsis polar glycerolipids in response to phosphorus starvation. Roles of phospholipases D zeta1 and D zeta2 in phosphatidylcholine hydrolysis and digalactosyldiacylglycerol accumulation in phosphorus-starved plants.

Phosphorus is an essential macronutrient that often limits plant growth and development. Under phosphorus-limited conditions, plants undergo substantial alterations in membrane lipid composition to cope with phosphorus deficiency. To characterize the changes in lipid species and to identify enzymes involved in plant response to phosphorus starvation, 140 molecular species of polar glycerolipids were quantitatively profiled in rosettes and roots of wild-type Arabidopsis (Arabidopsis thaliana) and phospholipase D knockout mutants pld zeta1, pld zeta2, and pld zeta1 pld zeta2. In response to phosphorus starvation, the concentration of phospholipids was decreased and that of galactolipids was increased. Phospholipid lost in phosphorus-starved Arabidopsis rosettes was replaced by an equal amount of galactolipid. The concentration of phospholipid lost in roots was much greater than in rosettes. Disruption of both PLD zeta1 and PLD zeta2 function resulted in a smaller decrease in phosphatidylcholine and a smaller increase in digalactosyldiacylglycerol in phosphorus-starved roots. The results suggest that hydrolysis of phosphatidylcholine by PLD zetas during phosphorus starvation contributes to the supply of inorganic phosphorus for cell metabolism and diacylglycerol moieties for galactolipid synthesis.

Arabidopsis↗
PubMed2006

Quantitative profiling of polar glycerolipid species from organs of wild-type Arabidopsis and a phospholipase Dalpha1 knockout mutant.

Lipid profiling is a targeted metabolomics platform that provides a comprehensive analysis of lipid species with high sensitivity. Profiling based on electrospray ionization tandem mass spectrometry (ESI-MS/MS) provides quantitative data and is adaptable to high throughput analyses. Here we report the profiling of 140 apparent molecular species of polar glycerolipids in Arabidopsis leaves, flower stalks, flowers, siliques, roots, and seeds. Considerable differences in lipid species occur among these organs, providing insights into the different lipid metabolic activities in a specific organ. In addition, comparative profiling between wild-type and a knockout mutant pldalpha1 (locus ID: AT3G15730) provides insight into the metabolic function of phospholipase D (PLD) in different organs. PLDalpha1 contributes significantly to phosphatidic acid (PA) levels in roots, seeds, flowers, and flower stalks, but little to basal PA levels in siliques and leaves. In seeds of the pldalpha1 mutant plants, levels of PA, lysophosphatidylcholine, and lysophosphatidylethanolamine were significantly lower than those of wild-type seeds, suggesting a role for PLDalpha1 in membrane lipid degradation in seeds.

Arabidopsis↗
PubMed2006

Malonaldehyde acts as a mitochondrial toxin: Inhibitory effects on respiratory function and enzyme activities in isolated rat liver mitochondria.

Malonaldehyde (MDA) is a product of oxidative damage to lipids, amino acids and DNA, and accumulates with aging and diseases. MDA can possibly react with amines to modify proteins to inactivity enzymes and also modify nucleosides to cause mutagenicity. Mitochondrial dysfunction is a major contributor to aging and age-associated diseases. We hypothesize that accumulated MDA due to mitochondrial dysfunction during aging targets mitochondrial enzymes to cause further mitochondrial dysfunction and contribute to aging and age-associated diseases. We investigated the effects of MDA on mitochondrial respiration and enzymes (membrane complexes I, II, III and IV, and dehydrogenases, including alpha-ketoglutaric dehydrogenase (KGDH), pyruvate dehydrogenase (PDH), malate dehydrogenase (MDH)) in isolated rat liver mitochondria. MDA showed a dose-dependent inhibition on mitochondrial NADH-linked respiratory control ratio (RCR) and ADP/O ratio declined from the concentrations of 0.2 and 0.8 micromol/mg protein, respectively, and succinate-linked mitochondrial RCR and ADP/O ratio declined from 1.6 and 0.8 micromol/mg protein. MDA also showed dose-dependent inhibition on the activity of PDH, KGDH and MDH significantly from 0.1, 0.2 and 2 micromol/mg protein, respectively. Activity of the complexes I and II was depressed by MDA at 0.8 and 1.6 micromol/mg protein. However, MDA did not affect activity of complexes III and IV in the concentration range studied (0-6.4 micromol/mg protein). These results suggest that MDA can cause mitochondrial dysfunction by inhibiting mitochondrial respiration and enzyme activity, and the sensitivity of the enzymes examined to MDA is in the order of PDH>KGDH>complexes I and II>MDH>complexes III and IV.

Aging↗
PubMed2006

An NADH-tetrazolium-coupled sensitive assay for malate dehydrogenase in mitochondria and crude tissue homogenates.

A sensitive spectrophotometric assay for determining mitochondrial malate dehydrogenase activity is described. The assay measures NADH production by coupling it to the reduction of 2-(p-iodophenyl)-3(p-nitrophenyl)-5-phenyl tetrazolium chloride (INT). Via an intermediate electron carrier, either phenazine methosulfate or lipoamide dehydrogenase, INT accepts electrons and is reduced to a red-colored formazan, which can be quantified by spectrophotometer at 500 nm. This assay uses only commercial reagents but gives a 2-5 fold (with lipoamide dehydrogenase) or 5-20 fold (with phenazine methosulfate) activity increase over currently available assays for pure enzyme in mitochondria isolated from human neuroblastoma cells, rat brain and liver, and crude homogenates of rat brain and liver. The assay can be easily performed with 96-well plate and less than 2.5 microg protein of isolated mitochondria or crude tissue homogenate. These results suggest that this assay is a simple, sensitive, stable and inexpensive method with wide application.

Animals↗
PubMed2006

A bifurcating pathway directs abscisic acid effects on stomatal closure and opening in Arabidopsis.

Terrestrial plants lose water primarily through stomata, pores on the leaves. The hormone abscisic acid (ABA) decreases water loss by regulating opening and closing of stomata. Here, we show that phospholipase Dalpha1 (PLDalpha1) mediates the ABA effects on stomata through interaction with a protein phosphatase 2C (PP2C) and a heterotrimeric GTP-binding protein (G protein) in Arabidopsis. PLDalpha1-produced phosphatidic acid (PA) binds to the ABI1 PP2C to signal ABA-promoted stomatal closure, whereas PLDalpha1 and PA interact with the Galpha subunit of heterotrimeric G protein to mediate ABA inhibition of stomatal opening. The results reveal a bifurcating signaling pathway that regulates plant water loss.

Abscisic Acid↗
PubMed2006

Signaling functions of phosphatidic acid.

Phosphatidic acid (PA) has emerged as a new class of lipid mediators involved in diverse cellular functions in plants, animals, and microorganisms. Considerable progress has been made recently on the production, cellular function, and mode of action of PA in the cell. The cellular levels of PA undergo dynamic changes in response to developmental and environmental stimuli. The production of signaling PA is mediated by families of multiple enzymes that regulate the timing, location, amount, and molecular species of PA. A number of PA target proteins have been identified, which include proteins involved in phosphorylation and dephosphorylation of proteins and lipids, as well as in G protein regulation, vesicular trafficking, and metabolism. PA mediates cellular functions through different modes of action, such as membrane tethering, modulation of enzymatic activities, and/or structural effects on cell membranes. The regulatory processes in which PA has been implicated include signaling pathways in cell growth, proliferation, reproduction, and responses to hormones and biotic and abiotic stresses.

Animals↗
PubMed2006

Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2.

The mechanisms underlying dopamine neuron loss in Parkinson's disease (PD) are not clearly defined. Here, we delineate a pathway by which dopaminergic loss induced by 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) is controlled in vivo. We reported previously that calpains play a central required role in dopamine loss after MPTP treatment. Here, we provide evidence that the downstream effector pathway of calpains is through cyclin-dependent kinase 5 (cdk5)-mediated modulation of the transcription factor myocyte enhancer factor 2 (MEF2). We show that MPTP-induced conversion of the cdk5 activator p35 to a pathogenic p25 form is dependent on calpain activity in vivo. In addition, p35 deficiency attenuates MPTP-induced dopamine neuron loss and behavioral outcome. Moreover, MEF2 is phosphorylated on Ser444, an inactivating site, after MPTP treatment. This phosphorylation is dependent on both calpain and p35 activity, consistent with the model that calpain-mediated activation of cdk5 results in phosphorylation of MEF2 in vivo. Finally, we provide evidence that MEF2 is critical for dopaminergic loss because "cdk5 phosphorylation site mutant" of MEF2D provides neuroprotection in an MPTP mouse model of PD. Together, these data indicate that calpain-p35-p25/cdk5-mediated inactivation of MEF2 plays a critical role in dopaminergic loss in vivo.

Animals↗
PubMed2006

Effect of a single overnight topical application of miconazole nitrate paste on acne papules.

BACKGROUND: The classical management of acne calls for prolonged oral and/or topical treatments; however, some patients request a rapid effect to make the papules disappear within a few hours or days. OBJECTIVE: To test the effect of a single overnight application of a paste containing 0.25% miconazole nitrate on acne papules, and comparison with the effect of the same but unmedicated paste. METHOD: Narrow-band reflectance spectroscopy was used to assess the changes in E index (erythema) after overnight application of the pastes. In the first study, a total of 117 acne papules were assessed in 15 adolescents. Measurements of the E index were performed at 24-h intervals for 4 days on acne papules and the surrounding normal-looking skin. The last two assessments were performed the mornings preceding and following, respectively, a single application of the medicated paste. The second part of the study consisted of a double-blind, split-face study on 25 adolescents with acne. They applied each of the two formulations on a randomized part of the forehead. A total of 161 acne papules received the medicated paste and 160 received the same but unmedicated paste. Measurements were performed the mornings before and after the overnight treatment. RESULTS: In the first part of the study, no significant daily difference was observed between the three series of pretreatment E indices, on both acne papules and normal skin. The treatment did not affect the E index of normal skin. By contrast, it decreased significantly the E index of the acne papules. The second part of the study also showed that the medicated paste significantly decreased the E index of acne papules. This effect was significantly (P < 0.05) superior to that of the unmedicated paste. CONCLUSION: A single overnight application of miconazole nitrate paste appears to reduce the erythematous aspect of acne papules.

Acne Vulgaris↗
PubMed2006

The mTOR pathway in the control of protein synthesis.

Signaling through mammalian target of rapamycin (mTOR) is activated by amino acids, insulin, and growth factors, and impaired by nutrient or energy deficiency. mTOR plays key roles in cell physiology. mTOR regulates numerous components involved in protein synthesis, including initiation and elongation factors, and the biogenesis of ribosomes themselves.

Animals↗
PubMed2005

Double knockouts of phospholipases Dzeta1 and Dzeta2 in Arabidopsis affect root elongation during phosphate-limited growth but do not affect root hair patterning.

Root elongation and root hair formation are important in nutrient absorption. We found that two Arabidopsis (Arabidopsis thaliana) phospholipase Ds (PLDs), PLDzeta1 and PLDzeta2, were involved in root elongation during phosphate limitation. PLDzeta1 and PLDzeta2 are structurally different from the majority of plant PLDs by having phox and pleckstrin homology domains. Both PLDzetas were expressed more in roots than in other tissues. It was reported previously that inducible suppression or inducible overexpression of PLDzeta1 affected root hair patterning. However, gene knockouts of PLDzeta1, PLDzeta2, or the double knockout of PLDzeta1 and PLDzeta2 showed no effect on root hair formation. The expression of PLDzetas increased in response to phosphate limitation. The elongation of primary roots in PLDzeta1 and PLDzeta2 double knockout mutants was slower than that of wild type and single knockout mutants. The loss of PLDzeta2, but not PLDzeta1, led to a decreased accumulation of phosphatidic acid in roots under phosphate-limited conditions. These results indicate that PLDzeta1 and PLDzeta2 play a role in regulating root development in response to nutrient limitation.

Arabidopsis↗