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Biomedical subjects

M Yu

Publications and source records attributed to M Yu.

At least 19 recordsLinked to original sources

Fourier-transform infrared-based genome-wide association study identifies candidate genes and variants for sow colostrum composition.

Sows with high prolificacy and better lactation traits are beneficial for weaned piglet number. Because the genetic basis of sow lactation traits remains elusive, genetic improvement for lactation traits lags behind that for litter traits, constraining the full realisation of genetic potential for large litters. Here, we measured 1&#xa0;060 Fourier-transform infrared (FTIR) wavenumbers and five predicted colostrum composition traits from sow colostrum samples. Heritability estimates for both the FTIR spectra and predicted traits ranged from moderate to high. Correlation analysis revealed that lactose percentage was negatively genetically correlated with the other four predicted traits (fat percentage, protein percentage, total solid content, and urea nitrogen content) and with 24&#xa0;h litter weight, which was positively genetically correlated with both protein and total solid content. Genome-wide association studies on the FTIR spectra and predicted traits identified 134 significant single-nucleotide polymorphisms (SNPs) (False discovery rate < 0.05), with most clustering on Sus scrofa chromosomes (SSC) 5 and 7. Among the candidate genes, two expressed in lactating mammary tissue have established roles in milk trait determination: (1) LALBA, which encodes a major colostrum protein and is responsible for lactose synthesis, and (2) BTN1A1, which mediates milk fat secretion. Additionally, the study detected two important candidate variants on SSC7: (1) rs691487382, which was colocalised with the expression quantitative trait locus signal for TRIM26 in the liver, a key metabolic organ supporting lactation, and (2) rs327923027, a missense variant located in a phylogenetically conserved domain of TRIM26, an E3 ubiquitin ligase implicated in liver homeostasis. Taken together, this study identifies, for the first time, candidate genes and variants for sow colostrum, providing genomic markers useful for genetic improvement.

Association analysis↗

Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells.

OBJECTIVE: Human adenovirus Ad-36 causes adiposity in animal models and enhances differentiation and lipid accumulation in human and 3T3-L1 preadipocytes, which may, in part, explain the adipogenic effect of Ad-36. We determined the consequences of Ad-36 infection on leptin and glucose metabolism in fat cells. DESIGN: 3T3-L1 preadipocytes were used to determine the effect of infection by human adenoviruses Ad-36, Ad-2, Ad-9 and Ad-37 on leptin secretion and lipid accumulation. Rat primary adipocytes were used to determine the effect of Ad-36 infection on leptin secretion and glucose uptake in vitro. Furthermore, the effect of Ad-36 on expressions of leptin and selected genes of de novo lipogenesis pathway of visceral adipose tissue were compared ex vivo, between Ad-36 infected and uninfected control rats. RESULTS: Ad-36 suppressed the expression of leptin mRNA in 3T3-L1 cells by approximately 58 and 52% on days 3 and 5 post-infection, respectively. Leptin release normalized to cellular lipid content was 51% lower (P<0.002) in the Ad-36 infected 3T3-L1 cells. Lipid accumulation was significantly greater and leptin secretion was lower for the 3T3-L1 cells infected with other human adenoviruses Ad-9, Ad-36, or Ad-37. Whereas, human adenovirus Ad-2 did not influence cellular lipid accumulation or the leptin release. In rat primary adipocytes, Ad-36 reduced leptin release by about 40% in presence of 0.48 (P<0.01) or 1.6 nM insulin (P<0.05) and increased glucose uptake by 93% (P<0.001) or 18% (P<0.05) in presence of 0 or 0.48 nM insulin, respectively. Next, the adipose tissue of Ad-36 infected rats showed two to fivefold lower leptin mRNA expression, and 1.6- to 21-fold greater expressions for acetyl Co-A carboxylase-1 and 1.2- to 6.3-fold greater expressions for fatty acid synthase, key genes of de novo lipogenesis, compared to the uninfected weight and adiposity matched controls. CONCLUSION: The in vitro and ex vivo studies show that Ad-36 modulates adipocyte differentiation, leptin production and glucose metabolism. Whether such a modulation contributes to enhanced adipogenesis and consequent adiposity in Ad-36 infected animals or humans needs to be determined.

3T3-L1 Cells↗

Core-shell structured SiO2@YVO4:Dy3+/Sm3+ phosphor particles: sol-gel preparation and characterization.

Spherical SiO(2) particles have been coated with YVO(4):Dy(3+)/Sm(3+) phosphor layers by a Pechini sol-gel process, leading to the formation of core-shell structured SiO(2)@YVO(4):Dy(3+)/Sm(3+) particles. X-ray diffraction (XRD), Fourier-transform IR spectroscopy, field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), photoluminescence (PL) spectra as well as lifetimes were used to characterize the resulting SiO(2)@YVO(4):Dy(3+)/Sm(3+) core-shell phosphors. The obtained core-shell phosphors have perfect spherical shape with narrow size distribution (average size ca. 300 nm), smooth surface and non-agglomeration. The thickness of shells could be easily controlled by changing the number of deposition cycles (20 nm for one deposition cycle). The core-shell particles show strong characteristic emission from Dy(3+) for SiO(2)@YVO(4):Dy(3+) and from Sm(3+) for SiO(2)@YVO(4):Sm(3+) due to an efficient energy transfer from YVO(4) host to them. The PL intensity of Dy(3+) and Sm(3+) increases with raising the annealing temperature and the number of coating cycles.

Gels↗

Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial.

BACKGROUND: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC). Clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the epidermal growth factor receptor (EGFR). Although, EGFR is not over-expressed in small cell lung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms. Agents that are active in NSCLC usually are also effective in SCLC. METHODS: The primary objective was to assess the clinical control rate: complete response (CR) partial response (PR) and stable disease (SD > 90 days), of gefitinib in patients with chemo-resistant and chemo-sensitive small cell cancers. Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function. Patients received gefitinib, 250 mg p.o. daily until disease progression or intolerable side effects. RESULTS: From April 2003 to March 2004, 19 patients were enrolled. Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma. Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen. Other patient characteristics: mean age 64 years (range 52-79 years); ECOG PS 0/1/2 = 7/9/3, M:F = 9:10. Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain. Four patients had grade four toxicities: one patient (5.3%) with fatigue and three patients (15.8%) with dyspnea. There were no patients with grade 3 or 4 rash or diarrhea. Two patients had stable disease (<90 days) and 17 had progressive disease as their best response. This study was a two-stage design and because the continuing criterion for stage one was not met, stage 2 was not performed. Median time to progression (TTP) was 50 days (95% CI = 21-58 days). One year overall survival (OS) was 21% (95% CI = 6-45.6%). CONCLUSION: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer.

Aged↗

Skin cancer after nonmyeloablative hematopoietic cell transplantation.

Squamous cell carcinoma (SCC) is the most common skin cancer in patients receiving immunosuppressive therapy, and is well documented to occur in patients that have undergone either solid organ transplantation or conventional myeloablative bone marrow transplantation. Nonmyeloablative hematopoietic cell transplantation (NMAT) provides transient, intensive immunosuppression, permitting allogeneic engraftment without ablating the marrow. The purpose of this report is to describe six patients that developed SCC (n=3), basal cell carcinoma (n=2), or malignant melanoma (n=2) over a period of 2-26 months following NMAT. All patients had myelodysplasia or acute myelogenous leukemia prior to transplantation. The authors demonstrate for the first time that patients who undergo NMAT are at risk for developing skin cancers and emphasize the need for close surveillance in the post transplantation period.

Basal Cell Carcinoma↗

Sequence identification, tissue distribution, mapping and polymorphism of the porcine sar1b gene.

The predicted full-length cDNA sequence of the porcine Sar1b gene was characterized by assembling pig ESTs from GenBank. The coding sequence (CDS) shares high sequence identity with the corresponding sequences of human (93%) and mouse (91%). The reverse transcription-polymerase chain reaction (RT-PCR) displayed that porcine Sar1b gene is expressed in all eight tissues (liver, small intestine, stomach, heart, lung, spleen, muscle and fat). Analysis of the somatic cell hybrid panel (SCHP) and the INRA-University of Minnesota porcine radiation hybrid (IMpRH) panel indicated the gene maps to SSC2 (1/2 q24)-q29 and most closely links to the interleukin-4 (IL4) gene. One base-pair deletion polymorphism in the 3' untranslated region (UTR) detected by PCR-single strand conformational polymorphism (PCR-SSCP) analysis shows allele frequency differences between Meishan, Yushan Black, Dahuabai, Qingping, Tibetan, Landrace, Large White and Duroc. The association analysis using pigs of Tongcheng, Landrace x (Large White x Tongcheng) and Large White x (Landrace x Tongcheng) suggested that the deletion polymorphism was associated with the porcine muscle pH value.

3' Untranslated Regions↗

Molecular cloning and characterization of pig, cow and sheep MAdCAM-1 cDNA and the demonstration of cross-reactive epitopes amongst mammalian homologues.

Full-length cDNA clones for the pig, cow and sheep mucosal addressin cellular adhesion molecule (MAdCAM)-1 homologues were isolated from Peyer's patches by a combination of reverse transcription (RT)-polymerase chain reaction and 5' and 3' RACE strategies. Degenerate primers based on conserved amino acid (aa) sequences within the N-terminal immunoglobulin (Ig)-like domains of the human and rodent MAdCAM-1 molecules were used for initial sequencing of the Ig-like domains. MAdCAM-1 transcripts of 1425 bp, 1525 bp and 1510 bp obtained for the pig, cow and sheep contained an open-reading frame for proteins of 390, 424 and 418 aa, respectively. The pig and ruminant MAdCAM-1 had two N-terminal Ig-like domains, a mucin-like region and a third Ig-like domain found in rodent but not human MAdCAM-1. Antibodies raised against bacterially expressed N-terminal Ig-like domains of pig, human and sheep MAdCAM-1 demonstrated the existence of cross-reactive epitopes, raising the possibility of producing monoclonal antibodies which can be used as multi-species MAdCAM-1-targeting reagent for the development of mucosal vaccines.

Amino Acid Sequence↗

Liver X receptor alpha and beta genes have the potential role on loin lean and fat content in pigs.

Liver X receptor alpha (LXRA) and beta (LXRB) are members of the nuclear receptor subfamily and are important regulators of genes involved in lipid, fatty acid and glucose metabolism in liver, and adipose tissue as well as in skeletal muscle. To investigate whether the two LXR genes play a role in influencing lean and fat growth in pigs, we discovered and examined two polymorphisms in LXRA (LXRA Bsl in exon 2, and LXRA HpyCH4 III in intron 8) and one polymorphism in LXRB (LXRB Aci I in exon 5) for genetic linkage and association analyses. Linkage analyses using a three-generation resource family of a cross between the Berkshire and Yorkshire (BY) pig breeds assigned LXRA to SSC2 and LXRB to SSC6. Association analyses were carried out among those polymorphisms and traits evaluated in the BY F(2) family and four pig commercial populations. These analyses indicated that the LXRA HpyCH4 III polymorphism was significantly associated with loin eye area and total lipid in individuals from the BY family. Significant associations were also found between Bsl I polymorphism in LXRA and boneless loin (%), as well as marbling score in one commercial line. The LXRB Aci I polymorphism was significantly associated with lean meat and fat content in the BY family and a number of the commercial lines examined. Our current findings suggested that LXRA and LXRB might have potential effects, especially for loin lean and fat content.

Adipose Tissue↗

Survival outcomes of resected patients who demonstrate a pathologic complete response after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer.

A variety of strategies, using chemotherapy, radiation therapy, and surgical resection have been employed in the treatment of locally advanced esophageal cancer. No strategy has proven superior, and poor long-term survival is anticipated. A survival benefit has been suggested for patients who achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation therapy. We examined the collective results at three institutions of patients who achieved a pCR following neoadjuvant chemoradiation therapy. A retrospective, chart-based review was conducted. Kaplan-Meier calculations were used to determine overall and disease-free survival. Between 1995 and 2002, 229 patients were treated with neoadjuvant chemoradiation followed by surgery as a planned approach for locally advanced esophageal cancer. Forty-one patients (18%) demonstrated pCR and were the focus of this study. Histology was adenocarcinoma in 29, squamous in 10, and adenosquamous/undifferentiated in two patients. Forty patients were staged by endoscopic ultrasound prior to neoadjuvant therapy and all demonstrated a T-stage of 2 or higher, while 19 had evidence of nodal metastasis. Four patients died in the perioperative period. The remaining patients have been followed for an average of 46 months. Overall survival at 5 years was 56.4% and a median survival has not been reached. Esophageal cancer patients who demonstrate a pCR following neoadjuvant chemoradiation are a select subset who demonstrate excellent long-term survival. Identification of clinical variables or biomarkers predictive of pCR may therefore optimize treatment strategies of patients with locally advanced esophageal cancer.

Adenocarcinoma↗

Sol-gel fabrication and photoluminescence properties of SiO2 @ Gd2O3:Eu3+ core-shell particles.

A uniform nanolayer of europium-doped Gd2O3 was coated on the surface of preformed submicron silica spheres by a Pechini sol-gel process. The resulted SiO2 @ Gd2O3:Eu3+ core-shell structured phosphors were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), photoluminescence (PL) spectra as well as kinetic decays. The XRD results show that the Gd2O3:Eu3+ layers start to crystallize on the SiO2 spheres after annealing at 400 degrees C and the crystallinity increases with raising the annealing temperature. The core-shell phosphors possess perfect spherical shape with narrow size distribution (average size: 640 nm) and non-agglomeration. The thickness of the Gd2O3:Eu3+ shells on the SiO2 cores can be adjusted by changing the deposition cycles (70 nm for three deposition cycles). Under short UV excitation, the obtained SiO2@Gd2O3:Eu3+ particles show a strong red emission with 5D0-7F2 (610 nm) of Eu3+ as the most prominent group. The PL intensity of Eu3+ increases with increasing the annealing temperature and the number of coating cycles.

Crystallization↗

New process control strategy for wastewater chlorination and dechlorination using ORP/pH.

Due to its efficiency and relatively low capital demanding, many wastewater treatment plants have applied chlorination for disinfection of treated wastewater before discharging it. However, determination of optimal doses of chlorine for chlorination and sulfite for dechlorination, which removes residual chlorine, should made to guarantee complete destruction of microorganisms in treated wastewater and to protect aquatic life in a receiving stream. In this study, a new ORP/pH based approach to determine endpoints of breakpoint chlorination and of dechlorinating titration and to optimize doses of chlorine and sulfite. In this new method, significant points on the ORP and pH profiles occurring during the titrations for chlorination and dechlorination were utilized to determine chlorine demand and sulfite dosage.

Chlorine↗

New ORP/pH based control strategy for chlorination and dechlorination of wastewater: pilot scale application.

Due to its efficiency and low capital demands, chlorination has been widely used for disinfection in many wastewater treatment plants. Since the oxidation power of free chlorine is bigger than combined chlorines which are formed from the reaction between chlorine and reducing agents in water (especially, NH4+ and organic nitrogen), for effective disinfection, excess amount of chlorine is added until all the reducing agents are oxidized and free chlorine is available. After chlorination, chlorine residues in wastewater are usually reduced with SO2 or sulfites before the treated wastewater is discharged, since they are toxic to aquatic life. Addition of excess amount of SO2 or sulfite should be avoided. Otherwise, they consume dissolved oxygen in a river or stream and may have adverse impact on the aquatic life. Determination of wastewater chlorine demand and of sulfite dosages for dechlorination has been a challenge to WWTP operators, due to the dynamic characteristics of wastewater. Recently, a new ORP/pH based approach to determine chlorine demand and sulfite dosage was proposed. The method utilizes significant points occurring on the pH and ORP profiles during chlorination and dechlorination titrations. In this study, the proposed automatic titration system has been implemented into a control system to optimize chlorine and sulfite doses for a pilot scale chlorination/dechlorination system. In short, the disinfection system with the pH/ORP based controller showed very successful results; complete inactivation of total coliforms, and almost zero residual chlorines and high DO in its effluent.

Chloramines↗

Characterization of epitopes for neutralizing monoclonal antibodies to classical swine fever virus E2 and Erns using phage-displayed random peptide library.

Infection of cells with classical swine fever virus (CSFV) is mediated by the interaction of envelope glycoproteins E2 and Erns with receptor molecules on the cell surface. These proteins are also the major antigens for eliciting neutralizing antibodies and conferring protective immunity. Here we report the identification of multiple neutralizing epitopes on these proteins by screening a phage-displayed random peptide library with CSFV-specific neutralizing monoclonal antibodies. Two different E2-specific neutralizing mAbs (a18 and 24/10) were found to bind to a common motif SPTxL, which is similar to the sequence SPTTL of the E2 protein (aa 289-293), indicating that this is likely to be an immunodominant epitope. Similarly, an immunodominant epitope corresponding to the sequence DKN of Erns (aa 117-119) was identified for two independent Erns-specific neutralizing antibodies, b4-22 and 24/16, respectively. Another binding motif, CxNNxTC, was identified for mAb 24/16, but not for b4-22. Sequencing analysis of the genes coding for the light chain of these mAbs was conducted to ensure that all mAbs were derived from different hybridomas, rather than from different subclones of a common parent line. Inhibition studies using immunofluorescent antibody assay and virus neutralization test demonstrated that the mimotope peptides truly mimicked the antibody binding determinants on the viral proteins. The detailed mapping data for these neutralizing epitopes will be useful for development of improved diagnostic tests and perhaps a peptide-based vaccine for this important swine disease.

Amino Acid Motifs↗

Lack of EGF receptor contributes to drug sensitivity of human germline cells.

Germline mutations have been associated with generation of various types of tumour. In this study, we investigated genetic alteration of germline tumours that affect the drug sensitivity of cells. Although all germline tumour cells we tested were hypersensitive to DNA-damaging drugs, no significant alteration was observed in their DNA repair activity or the expression of DNA repair proteins. In contrast, germline tumours expressed very low level of epidermal growth factor receptor (EGFR) compared to drug-resistant ovarian cancer cells. An immunohistochemical analysis indicated that most of the primary germline tumours we tested expressed very low level of EGFR. In accordance with this, overexpression of EGFR in germline tumour cells showed an increase in drug resistance, suggesting that a lack of EGFR, at least in part, contributes to the drug sensitivity of germline tumours.

Blotting, Western↗