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1.
Article in Zh | MEDLINE | ID: mdl-37667150

ABSTRACT

Objective: To investigate the role of ferroptosis in testicular injury in adolescent male mice induced by TDCIPP. Methods: In December 2021, 30 healthy 3-week-old male C57BL/6 mice, with a body weight of (13±2) g, were selected and fed adaptive for one week. They were divided into control group, low-dose group, medium-dose group, high-dose group and iron death inhibitor group according to a random number table, with 6 mice in each group. Mice in low, medium and high dose groups were treated with 5, 25 and 125 mg/ (kg·d) TDCIPP for 28 days, respectively, while the control group was treated with the same amount of corn oil for 28 days. The iron death inhibitor group was given 125 mg/ (kg·d) TDCIPP intragastric administration for 28 days, and 30 mg/kg DFO saline solution was intraperitoneally injected three times a week. After the treatment, the mice were killed, the epididymis was separated, and sperm count was performed. HE staining was used to observe the morphological changes of mouse testis, and iron content in testis was detected by tissue iron detection kit. The level of reactive cxygen species, MDA content, and the mitochondrial membrane potential level of mice were detected. Western blot analysis of testicular glutathione peroxidase (GPX4) and internal cyclooxygenase-2 (COX2) protein expression. Results: Compared with the control group, the spermatogenic cells in the testes of mice treated with medium-and high-dose of TDCIPP were disorderly arranged, showing a vacuolar structure. the number of sperm in the epididymis was significantly reduced (P=0.009, 0.004), while the sperm deformity rate was significantly increased (P=0.010, 0.000). Moreover, the content of ROS, iron ion and MDA in the testes increased significantly (P<0.05), and the mitochondrial membrane potential of mouse testicular cells decreased significantly (P<0.05). The expression of GPX4 proteins decreased (P<0.05). while the expression of COX2 increased significantly (P<0.01). Compared with high-dose group group, spermatogenic cells in ferroptosis inhibitor group were closely arranged and normal, and ROS and Fe contents in testicular tissue were significantly decreased (P<0.01) ; GPX4 protein expression was significantly increased while COX2 protein expression was significantly decreased (P<0.05) . Conclusion: Ferroptosis is involved in TDCIPP-induced testicular damage in male pubertal mice.


Subject(s)
Ferroptosis , Male , Animals , Mice , Mice, Inbred C57BL , Cyclooxygenase 2 , Reactive Oxygen Species , Semen , Glutathione Peroxidase , Iron
3.
Occup Med (Lond) ; 68(9): 587-592, 2018 Dec 26.
Article in English | MEDLINE | ID: mdl-30423151

ABSTRACT

BACKGROUND: Cleaning agents have been commonly implicated as causative or triggering factors in work-related asthma (WRA), mainly from epidemiologic studies. Relatively few clinical series have been reported. AIMS: We aimed to compare socio-demographic and clinical features among tertiary clinic patients with WRA exposed to cleaning and non-cleaning products. METHODS: Analyses were conducted on a patient database containing 208 patients with probable WRA referred to the asthma and airway centre at a tertiary centre hospital in Canada from 2000 to 2014. Chi-squared and independent samples t-tests were used to analyse categorical and continuous data, respectively. RESULTS: Twenty-two (11%) WRA cases were attributed to a variety of cleaning product exposures, 12 were diagnosed as occupational asthma (OA) and 10 as work-exacerbated asthma (WEA) (10% of all OA and 11% of all WEA). There were multiple exposures and the responsible agent(s) could seldom be clearly identified. Most frequent categories of exposure were surfactants, alcohols, disinfectants and acids. Compared to WRA with other exposures, those with cleaning agent exposures had a significantly larger proportion of females (82 versus 35%, P < 0.001), included a higher percentage of workers in healthcare (41 versus 4%, P < 0.001), and submitted more workers' compensation claims (86 versus 64%, P = 0.05). Other characteristics were comparable. CONCLUSIONS: In a tertiary referral clinic, patients with WRA from cleaning agent exposure had clinical characteristics that were similar to those with WRA from other causes. Most frequent exposures were surfactants, alcohols, disinfectants and acids.


Subject(s)
Asthma, Occupational/etiology , Detergents/adverse effects , Adult , Asthma, Occupational/complications , Asthma, Occupational/epidemiology , Chi-Square Distribution , Female , Humans , Male , Middle Aged , Occupational Exposure/adverse effects , Risk Factors , Workplace/standards , Workplace/statistics & numerical data
4.
BMC Genomics ; 17(1): 1049, 2016 12 21.
Article in English | MEDLINE | ID: mdl-28003017

ABSTRACT

BACKGROUND: Enterohaemorrhagic Escherichia coli (EHEC), like E. coli O157:H7 are frequently detected in bovine faecal samples at slaughter. Cattle do not show clinical symptoms upon infection, but for humans the consequences after consuming contaminated beef can be severe. The immune response against EHEC in cattle cannot always clear the infection as persistent colonization and shedding in infected animals over a period of months often occurs. In previous infection trials, we observed a primary immune response after infection which was unable to protect cattle from re-infection. These results may reflect a suppression of certain immune pathways, making cattle more prone to persistent colonization after re-infection. To test this, RNA-Seq was used for transcriptome analysis of recto-anal junction tissue and ileal Peyer's patches in nine Holstein-Friesian calves in response to a primary and secondary Escherichia coli O157:H7 infection with the Shiga toxin (Stx) negative NCTC12900 strain. Non-infected calves served as controls. RESULTS: In tissue of the recto-anal junction, only 15 genes were found to be significantly affected by a first infection compared to 1159 genes in the ileal Peyer's patches. Whereas, re-infection significantly changed the expression of 10 and 17 genes in the recto-anal junction tissue and the Peyer's patches, respectively. A significant downregulation of 69 immunostimulatory genes and a significant upregulation of seven immune suppressing genes was observed. CONCLUSIONS: Although the recto-anal junction is a major site of colonization, this area does not seem to be modulated upon infection to the same extent as ileal Peyer's patches as the changes in gene expression were remarkably higher in the ileal Peyer's patches than in the recto-anal junction during a primary but not a secondary infection. We can conclude that the main effect on the transcriptome was immunosuppression by E. coli O157:H7 (Stx-) due to an upregulation of immune suppressive effects (7/12 genes) or a downregulation of immunostimulatory effects (69/94 genes) in the ileal Peyer's patches. These data might indicate that a primary infection promotes a re-infection with EHEC by suppressing the immune function.


Subject(s)
Cattle Diseases/immunology , Cattle Diseases/microbiology , Escherichia coli Infections/veterinary , Escherichia coli O157/immunology , Host-Pathogen Interactions/immunology , Immunosuppression Therapy , Animals , Cattle , Cattle Diseases/genetics , Cattle Diseases/metabolism , Computational Biology/methods , Escherichia coli O157/genetics , Escherichia coli O157/metabolism , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Gene Regulatory Networks , Immunity, Innate , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Peyer's Patches/cytology , Peyer's Patches/immunology , Peyer's Patches/metabolism , Transcriptome
5.
Genet Mol Res ; 15(1)2016 Jan 22.
Article in English | MEDLINE | ID: mdl-26909916

ABSTRACT

Recurrent spontaneous abortions (RSAs) occur in approximately 15 to 20% of all clinically recognizable pregnancies. Structural chromosome abnormalities result in increased risk of pregnancy loss. Parental chromosomal abnormalities are an important genetic cause of RSAs. Some cytogenetic investigations have been performed in various countries and regions to determine the pattern of chromosomal abnormalities in parents with RSAs. The aim of this study was to report the prevalence and type of structural chromosomal abnormalities in couples in cases of RSAs in Jilin Province, China. The prevalence of structural chromosomal abnormalities in these couples was 2.98%. The number of female carriers with balanced chromosomal aberrations significantly exceeded that of such male carriers, and the ratio of female/male carriers was approximately 2:1. The number of abortions in the case of female carriers was more than that for male carriers before the structural chromosome abnormality was diagnosed. This indicates that genetic counseling for couples with structural chromosomal abnormalities should consider the gender of the carriers.


Subject(s)
Abortion, Habitual/genetics , Chromosome Aberrations/statistics & numerical data , Abortion, Habitual/epidemiology , Adult , China/epidemiology , Female , Humans , Male , Prevalence , Sex Factors , Young Adult
6.
Genet Mol Res ; 14(3): 10897-904, 2015 Sep 10.
Article in English | MEDLINE | ID: mdl-26400317

ABSTRACT

Klinefelter syndrome (KS) is the most common genetic cause of male infertility. Widespread development in assisted reproductive technology has provided non-mosaic KS patients with the opportunity of having biological children. Testosterone replacement therapy and micro-dissection testicular sperm extraction are effective sperm retrieval techniques for KS patients. Despite the success of sperm retrieval and intracytoplasmic sperm injection (ICSI), some areas of early aggressive hormonal spermatogenesis and appropriate management of KS remain controversial. Androgenotherapy, a common treatment for KS, carries a risk of decreasing focal spermatogenesis by lowering the gonadotropin content. Inadequately treated hypogonadism increases psychosocial morbidity in KS patients. Preventive care must be provided from the time of diagnosis, preferentially through a multidisciplinary approach. This indicates the need for improved genetic counseling of KS patients. The aim of this study was to report the prevalence of non-mosaic KS in a Chinese infertile male population. The rate of early diagnosis was lower in KS patients; most of these were diagnosed after rising concerns of reproductive capacity. The mean age of patients with sperm or germ cells was significantly lower, while the semen volume of these patients was significantly higher. However, the semen volume was negatively correlated with the age and ratio of luteinizing hormone/testosterone content in KS patients. Therefore, genetic counseling of KS patients should focus on early diagnosis and timely treatment, in addition to improving the quality of life of all KS patients. The use of testosterone replacement therapy and/ or micro-dissection testicular sperm extraction should be preferentially considered for fertility preservation.


Subject(s)
Genetic Counseling/methods , Klinefelter Syndrome/diagnosis , Klinefelter Syndrome/therapy , Adult , China , Hormone Replacement Therapy , Humans , Infertility, Male/genetics , Infertility, Male/physiopathology , Infertility, Male/therapy , Karyotype , Klinefelter Syndrome/genetics , Klinefelter Syndrome/physiopathology , Luteinizing Hormone/blood , Male , Quality of Life , Reproductive Techniques, Assisted , Sperm Retrieval , Spermatogenesis/genetics , Testosterone/administration & dosage , Testosterone/blood
7.
Genet Mol Res ; 14(4): 16178-84, 2015 Dec 08.
Article in English | MEDLINE | ID: mdl-26662410

ABSTRACT

Chromosomal abnormality is the most common genetic cause of male infertility, particularly in cases of azoospermia, oligozoospermia, and recurrent spontaneous abortion. Chromosomal rearrangement may interrupt an important gene or exert position effects. The functionality of genes at specific breakpoints, perhaps with a specific role in spermatogenesis, may be altered by such rearrangements. Structural chromosome abnormalities are furthermore known to increase the risk of pregnancy loss. In this study, we aimed to assess chromosomal defects in infertile men from Jilin Province, China, by genetic screening and to evaluate the relationship between structural chromosome abnormalities and male infertility. The prevalence of chromosomal abnormalities among the study participants (receiving genetic counseling in Jilin Province, China) was 10.55%. The most common chromosome abnormality was Klinefelter syndrome, and the study findings suggested that azoospermia and oligospermia may result from structural chromosomal abnormalities. Chromosome 1 was shown to be most commonly involved in male infertility and balanced chromosomal translocation was identified as one of the causes of recurrent spontaneous abortion. Chromosomes 4, 7, and 10 were the most commonly involved chromosomes in male partners of women experiencing repeated abortion.


Subject(s)
Chromosome Aberrations , Genetic Testing , Infertility, Male/diagnosis , Infertility, Male/genetics , Adolescent , Adult , Azoospermia/diagnosis , Azoospermia/epidemiology , Azoospermia/genetics , China/epidemiology , Genetic Counseling , Genetic Testing/methods , Humans , Infertility, Male/epidemiology , Karyotype , Karyotyping , Male , Mass Screening , Middle Aged , Oligospermia/diagnosis , Oligospermia/epidemiology , Oligospermia/genetics , Semen Analysis , Young Adult
8.
Nanotechnology ; 25(42): 425204, 2014 Oct 24.
Article in English | MEDLINE | ID: mdl-25274278

ABSTRACT

Exploring the role of electrode metals on the resistive switching properties of metal electrode/oxide/metal electrode sandwiched structures provides not only essential information to understand the underlying switching mechanism of the devices, but also useful guidelines for the optimization of the switching performance. A systematic study has been performed to investigate the influence of electrodes on the resistive switching characteristics of zinc oxide (ZnO) films in this contribution, in terms of both the intrinsic and interfacial effects. It has been found that the low-resistance state resistances (Ω(LRS)) of all the investigated devices are below 50 Ω, which can be attributed to the formation of highly conductive channels throughout the ZnO films. On the other hand, the high-resistance state resistances (Ω(HRS)) depend on the electronegativity and ionic size of the employed electrode metals. Devices with electrode metals of high electronegativity and large ionic size possess high Ω(HRS) values, while those with electrode metals of low electronegativity and small ionic size carry low Ω(HRS) values. A similar trend of the set voltages has also been observed, while the reset voltages are all distributed in a narrow range close to ±0.5 V. Moreover, the forming voltages of the switching devices strongly depend on the roughness of the metal/ZnO and/or ZnO/metal interface. The present work provides essential information for better understanding the switching mechanism of zinc oxide based devices, and benefits the rational selection of proper electrode metals for the device performance optimization.

9.
Anim Genet ; 45 Suppl 1: 40-50, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24990294

ABSTRACT

This report presents a study utilizing next-generation sequencing technology, combined with chromatin immunoprecipitation (ChIP-seq) technology to analyze histone modification induced by butyrate and to construct a high-definition map of the epigenomic landscape with normal histone H3 and H4 and their variants in bovine cells at the whole-genome scale. A total of 10 variants of histone H3 and H4 modifications were mapped at the whole-genome scale (acetyl-H3K18-ChIP-seq, trimethy-H3K9, histone H4 ChIP-seq, acetyl-H4K5 ChIP-seq, acetyl-H4K12 ChIP-seq, acetyl-H4K16 ChIP-seq, histone H3 ChIP-seq, acetyl H3H9 ChIP-seq, acetyl H3K27 ChIP-seq and tetra-acetyl H4 ChIP-seq). Integrated experiential data and an analysis of histone and histone modification at a single base resolution across the entire genome are presented. We analyzed the enriched binding regions in the proximal promoter (within 5 kb upstream or at the 5'-untranslated region from the transcriptional start site (TSS)), and the exon, intron and intergenic regions (defined by regions 25 kb upstream and 10 kb downstream from the TSS). A de novo search for the binding motif of the 10 ChIP-seq datasets discovered numerous motifs from each of the ChIP-seq datasets. These consensus sequences indicated that histone modification at different locations changes the histone H3 and H4 binding preferences. Nevertheless, a high degree of conservation in histone binding also was presented in these motifs. This first extensive epigenomic landscape mapping in bovine cells offers a new framework and a great resource for testing the role of epigenomes in cell function and transcriptomic regulation.


Subject(s)
Butyrates/pharmacology , Cattle/genetics , Epigenomics/methods , Genome/drug effects , Genome/genetics , Histones/metabolism , Animals , Chromatin Immunoprecipitation/veterinary , High-Throughput Nucleotide Sequencing/methods , High-Throughput Nucleotide Sequencing/veterinary , Histones/drug effects
10.
J Dairy Sci ; 97(7): 4193-207, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24767884

ABSTRACT

Molecular mechanisms regulating rumen epithelial development remain largely unknown. To identify gene networks and regulatory factors controlling rumen development, Holstein bull calves (n=18) were fed milk replacer only (MRO) until 42 d of age. Three calves each were euthanized at 14 and 42 d of age for tissue collection to represent preweaning, and the remaining calves were provided diets of either milk replacer + orchard grass hay (MH; n=6) to initiate weaning without development of rumen papillae, or milk replacer + calf starter (MG; n=6) to initiate weaning and development of rumen papillae. At 56 and 70 d of age, 3 calves from the MH and MG groups were euthanized for collection of rumen epithelium. Total RNA and protein were extracted for microarray analysis and to validate detected changes in selected protein expression, respectively. As expected, calves fed MRO had no rumen papillae and development of papillae was greater in MG versus MH calves. Differentially expressed genes between the MRO diet at d 42 (preweaning) versus the MG or MH diets at d 56 (during weaning) were identified using permutation analysis of differential expression. Expression of 345 and 519 transcripts was uniquely responsive to MG and MH feeding, respectively. Ingenuity Pathway Analysis (Qiagen, Redwood City, CA) indicated that the top-ranked biological function affected by the MG diet was the cell cycle, and TFGB1, FBOX01, and PPARA were identified as key transcriptional regulators of genes responsive to the MG diet and associated with development of rumen papillae. Increased expressions of TGFB1 mRNA and protein in response to the MG diet were confirmed by subsequent analyses. The top-ranking biological function affected by the MH diet was energy production. Receptors for IGF-1 and insulin, ESRRA, and PPARD were identified by ingenuity pathway analysis as transcriptional regulators of genes responsive to the MH diet. Further analysis of TGFB1 and ESRRA mRNA expression in rumen epithelium obtained from a separate ontogenic study of Holstein calves (n=26) euthanized every 7d from birth to 42 d of age showed increases in transcript expression with advancing age, supporting their roles in mediating rumen epithelial development and function during weaning. Additional evaluation of gene expression in the rumen epithelium of adult cows ruminally infused with butyrate also suggested that observed changes in ESRRA mRNA expression in developing calf rumen may be mediated by increased butyrate concentration. Our results identify TGFB1 and ESRRA as likely transcriptional regulators of rumen epithelial development and energy metabolism, respectively, and provide targets for modulation of rumen development and function in the growing calf.


Subject(s)
Cattle/growth & development , Gene Expression Regulation, Developmental , Receptors, Estrogen/genetics , Transforming Growth Factor beta1/genetics , Weaning , Animals , Cattle/genetics , Cattle/metabolism , Epithelium/growth & development , Epithelium/metabolism , Gastric Mucosa/growth & development , Gastric Mucosa/metabolism , Gene Regulatory Networks , Genome , Male , Receptors, Estrogen/metabolism , Rumen/growth & development , Rumen/metabolism , Transforming Growth Factor beta1/metabolism , ERRalpha Estrogen-Related Receptor
11.
Zhonghua Xue Ye Xue Za Zhi ; 43(1): 26-30, 2022 Jan 14.
Article in Zh | MEDLINE | ID: mdl-35231989

ABSTRACT

Objective: To analyze the clinical characteristics, laboratory examination, diagnosis, treatment, and outcome of hereditary factor Ⅹ (FⅩ) deficiency. Methods: Clinical data of 11 patients with congenital FⅩ deficiency were retrospectively analyzed from July 2009 to February 2021. Results: There were 3 males and 8 females. Median age was 39 (5-55) years. The media duration of follow-up was 81.67 (1.87-142.73) months. Of the 11 patients, 10 had bleeding symptoms, 7 had ecchymosis or hemorrhage after skin bump, 7 had nosebleed, 6 had gingival hemorrhage, and 1 had muscle hematoma. Among the female patients, 6 had menorrhagia and 1 experienced bleeding after vaginal delivery. Family history of FⅩ deficiency was found in one case. Eight patients had a history of surgery, and four had postoperative bleeding. Laboratory findings were characterized by significantly prolonged activated partial thromboplastin time, prothrombin time, and decreased FⅩ activity (FⅩ∶C) . Four cases underwent gene mutation analysis and five new mutations were found. Four cases were treated with prothrombin complex concentrates (PCC) and seven cases with fresh frozen plasma (FFP) . One female patient had significantly reduced menstrual volume after PCC prophylactic therapy. One patient received FFP for prophylactic infusion with no bleeding during and after the operation. Conclusion: Most patients with congenital FⅩ deficiency had bleeding symptoms and there was no significant correlation between severity of bleeding symptoms and FⅩ∶C. Prophylaxis should be applied in patients with severe bleeding tendencies. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of congenital FX deficiency.


Subject(s)
Factor X Deficiency , Adolescent , Adult , Blood Coagulation Factors/therapeutic use , Blood Coagulation Tests , Child , Child, Preschool , Factor X Deficiency/genetics , Female , Hemorrhage/drug therapy , Humans , Male , Middle Aged , Plasma , Retrospective Studies , Young Adult
12.
Parasite Immunol ; 33(12): 669-78, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21958368

ABSTRACT

Galectin-11 (LGALS11) has been suggested to play an important role in protective immunity against gastrointestinal nematodes in ruminants. However, in cattle, this molecule has not been characterized in detail. In the current study, it was shown that transcription of LGALS11 was highly inducible in the bovine abomasal mucosa after an Ostertagia ostertagi infection. LGALS11 protein expression was also increased in the abomasal mucosa following O. ostertagi infection and localized to the nucleus and cytoplasm of epithelial cells and the mucus. Using in vitro abomasal epithelial cell cultures, it was shown that LGALS11 induction was associated with the proliferative and dedifferentiated status of cells. However, LGALS11 was not induced following stimulation with O. ostertagi excretory-secretory products. These results suggest that LGALS11 induction in vivo may be an indirect rather than a direct effect of the parasite on the epithelium. In addition, LGALS11 transcript was also detected in the abomasal lymph nodes where it was shown to be transcribed in MHCII+ cells; however, transcription levels in the lymph nodes were not altered after O. ostertagi infection. In addition, LGALS11 was also induced in the small intestine by different types of parasites, including the nematode Cooperia oncophora and the protozoan parasite Giardia duodenalis.


Subject(s)
Cattle Diseases/immunology , Cattle Diseases/parasitology , Galectins/biosynthesis , Gastrointestinal Tract/immunology , Gastrointestinal Tract/parasitology , Ostertagiasis/veterinary , Animals , Cattle , Cell Proliferation , Cells, Cultured , Epithelial Cells/immunology , Gene Expression Profiling , Intestinal Mucosa/immunology , Ostertagia/immunology , Ostertagia/pathogenicity , Ostertagiasis/immunology , Rumen/immunology
13.
Transl Psychiatry ; 9(1): 10, 2019 01 16.
Article in English | MEDLINE | ID: mdl-30664741

ABSTRACT

Antidepressants are among the most-prescribed class of drugs in the world and though weight gain is a common outcome of antidepressant treatment, that effect is not well understood. We employed an animal model comprised of 2 weeks of chronic restraint stress with antidepressant treatment, followed by diet-induced obesity. We showed that short-term antidepressant treatment had long-lasting effects, not only leading to weight gain, but also enhancing trabecular and cortical bone features in rats; therefore, weight gain in this model was different from that of the classic diet-induced obesity. Late in the post-restraint recovery period, antidepressant-treated animals were significantly heavier and had better bone features than saline-treated controls, when assessed in the distal femoral metaphysis. The propensity to gain weight might have influenced the rate of catch-up growth and bone allometry, as heavier animals treated with fluoxetine also had enhanced bone features when compared to non-stressed animals. Therefore, short-term antidepressant treatment ameliorated the long-term effects of stress on body growth and bone. Growth and bone structural features were associated with leptin levels, and the interaction between leptin levels and antidepressant was significant for bone mineral content, suggesting that short-term antidepressants in the context of long-term diet-induced obesity modified the role of leptin in bone formation. To our knowledge this is the first study reporting that short-term antidepressant treatment has long-lasting effects in restoring the effects of chronic stress in body weight and bone formation. Our findings may be relevant to the understanding and treatment of osteoporosis, a condition of increasing prevalence due to the aging population.


Subject(s)
Antidepressive Agents/pharmacology , Bone Density/drug effects , Stress, Psychological/drug therapy , Weight Gain/drug effects , Animals , Behavior, Animal/drug effects , Disease Models, Animal , Fluoxetine/pharmacology , Leptin/metabolism , Male , Obesity/metabolism , Rats , Rats, Sprague-Dawley
14.
Anim Genet ; 39(6): 655-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18699832

ABSTRACT

We present a detailed breakpoint mapping and population frequency analysis of a 214-kb microdeletion that removes multiple olfactory receptor genes. Using progressive rounds of PCR assays, we mapped the upstream and downstream breakpoints of this microdeletion event to approximately 1 and 12 kb genomic regions, respectively. We developed PCR-based genotyping assays, characterized a dairy cattle panel of 96 samples and found that the frequency of the deletion allele was over 51%. Our results indicated that this microdeletion is an ancient event occurring in one of the earlier founders, and that it has been stably inherited across generations in the North American dairy cattle population.


Subject(s)
Cattle/genetics , Gene Deletion , Polymorphism, Genetic , Animals , Dairying , Genome , Polymerase Chain Reaction
15.
Dev Biol (Basel) ; 132: 391-398, 2008.
Article in English | MEDLINE | ID: mdl-18817332

ABSTRACT

The modern version of epigenetics includes the molecular mechanisms that influence the phenotypic outcome of a gene or genome, in absence of changes to the underlying DNA sequence. A host of genomic interrelationships with the diet evidently exist. The broad topic of nutrigenomics is defined as the interaction between nutrition and an individual's genome. Ruminant species have evolved to metabolize the short-chain volatile fatty acids (VFAs, acetate, propionate, and butyrate) to fulfill up to 70% of their nutrient energy requirements. The potential biological roles of VFAs were investigated using the established Madin-Darby bovine kidney epithelial cell line. Butyrate induces cell cycle arrest and apoptosis in bovine cells. Gene expression profiling indicated that butyrate induces many significant changes in the expression of genes associated with regulatory pathways that are critical to cell growth, immune response and signal transduction. Functional category and pathway analyses of the microarray data revealed that several canonical pathways (the cell cycle G2/M DNA damage checkpoint and G1/S checkpoint regulation; pyrimidine metabolism; and purine metabolism insulin-like growth factor axis components) were significantly affected.


Subject(s)
Epigenesis, Genetic , Animals , Apoptosis/drug effects , Butyric Acid/pharmacology , Cattle , Cell Line , Flow Cytometry
16.
Dev Biol (Basel) ; 132: 231-237, 2008.
Article in English | MEDLINE | ID: mdl-18817307

ABSTRACT

As a complement to the Bovine HapMap Consortium project, we initiated a systematic study of the copy numbervariation (CNV) within the same cattle population using array comparative genomic hybridization (array CGH). Oligonucleotide CGH arrays were designed and fabricated to cover all chromosomes with an average interval of 6 kb using the latest bovine genome assembly. In the initial screening, three Holstein bulls were selected to represent major paternal lineages of the Holstein breed with some maternal linkages between these lines. Dual-label hybridizations were performed using either Hereford L1 Dominette 01449 or L1 Domino 99375 as reference. The CNVs were represented by gains and losses of normalized fluorescence intensities relative to the reference. The data presented here, for the first time, demonstrated that significant amounts of germline and fewer somatic CNVs exist in cattle, that many CNVs are common both across diverse cattle breeds and among individuals within a breed, and that array CGH is an effective tool to systematically detect bovine CNV. Selected CNVs have been confirmed by independent methods using real-time (RT) PCR. The strategy used in this study, based on genome higher-orderarchitecture variation, is a powerful approach to generating resources for the identification of novel genomic variation and candidate genes for economically important traits.


Subject(s)
Germ Cells , Mutation , Animals , Base Sequence , Cattle , DNA Primers , Genotype , Nucleic Acid Hybridization , Polymorphism, Single Nucleotide
17.
J Dairy Sci ; 90 Suppl 1: E55-65, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17517752

ABSTRACT

It is well established that estrogen is required for mammary epithelial cell proliferation and ductal development in the growing animal, and that lobuloalveolar development during gestation is dependent on progesterone. The effects of these steroid hormones on gene expression in the mammary gland are mediated primarily by their respective nuclear hormone receptors, which function as hormone-bound transcription factors. To gain insight into how estrogen and progesterone regulate mammary gland growth and function in cattle, we and others have characterized the expression patterns of their cognate nuclear hormone receptors in the bovine mammary gland throughout development, pregnancy, and lactation. This work has identified a lack of expression of estrogen receptor beta and a greater abundance of progesterone receptor during lactation in the bovine mammary gland, compared with the rodent gland. We speculate that interactions among the estrogen receptor isoforms that regulate progesterone receptor expression may contribute to these species differences. Further, demonstrated expression of substantial quantities of estrogen receptor within the prepubertal bovine mammary fat pad, along with coordinated insulin-like growth factor-I expression, suggests that this tissue may stimulate parenchymal growth via an estrogen-responsive paracrine mechanism. In addition, the recent availability of bovine genomic sequence information and microarray technologies has permitted the study of global gene expression in the mammary gland in response to the steroid environment. We have identified more than 100 estrogen-responsive genes, of which the majority are novel estrogen gene targets. Estrogen-induced changes in gene expression were consistent with increased mammary epithelial cell proliferation, increased extracellular matrix turnover in parenchyma, and increased extracellular matrix deposition in the fat pad. A comparison of estrogen-responsive genes in the mammary glands of humans, mice, and cattle suggests considerable variation among species, as well as potential differences in regulatory elements in common estrogen receptor gene targets. Continuing studies using advanced molecular techniques should assist in elucidating the complex regulation of mammary function at the transcript level.


Subject(s)
Gene Expression Regulation , Lactation/metabolism , Mammary Glands, Animal/metabolism , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Animals , Cattle , Estrogens/metabolism , Estrogens/physiology , Female , Mammary Glands, Animal/growth & development , Microarray Analysis , Pregnancy , Progesterone/metabolism , Progesterone/physiology , Protein Isoforms/analysis , Protein Isoforms/genetics , Receptors, Estrogen/genetics , Receptors, Progesterone/genetics
18.
Int J Parasitol ; 45(9-10): 637-46, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25937360

ABSTRACT

Recently we reported the successful vaccination of calves against Cooperia oncophora with a double domain activation-associated secreted protein, purified from the excretory-secretory material of adult stage parasites. In an attempt to elucidate the immune mechanisms involved in protection, the humoral and cell-mediated immune responses following vaccination and infection were compared with non-vaccinated control animals. Antigen-specific IgG1, IgG2 and IgA levels were significantly increased in sera of vaccinated animals post vaccination, whereas no effect was observed for IgM. Antigen-specific intestinal IgG1 levels were significantly increased in the vaccinated animals, whereas no differences were observed for antigen-specific IgA, IgM and IgG2 levels. Upon re-stimulation in vitro with the vaccine antigen, a significant proliferation of both αß- and γδ-T cells, and B cells, collected from mesenteric lymph nodes, was only observed in vaccinated animals. RNA-seq analysis of intestinal tissue yielded a list of 67 genes that were differentially expressed in vaccinated animals following challenge infection, amongst which were several cell adhesion molecules, lectins and glycosyl transferases. A correlation analysis between all immunological and parasitological parameters indicated that intestinal anti-double domain activation-associated secreted protein IgG1 levels correlated negatively with cumulative faecal egg counts and positively with the proportion of L4s and L5s. The proportion of immature stages was also positively correlated with the proliferation of αß T cells. Worm length was negatively correlated with the transcript levels of several lectins and cell adhesion molecules. Overall, the results indicate that intramuscular administration of the vaccine resulted in an immune memory response particularly characterised by increased antigen-specific IgG1 levels in the intestinal mucosa.


Subject(s)
Cattle Diseases/prevention & control , Trichostrongyloidea/immunology , Trichostrongyloidiasis/veterinary , Vaccines/immunology , Animals , Antibodies, Helminth/blood , Antibody Specificity , Antigens, Helminth/immunology , Cattle , Gene Expression Regulation/immunology , Immunoglobulin A/blood , Immunoglobulin G/blood , Injections, Intramuscular , Male , Trichostrongyloidiasis/prevention & control , Vaccination
19.
Eur J Surg Oncol ; 41(8): 958-66, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26054706

ABSTRACT

BACKGROUND: In early breast cancer patients with sentinel node metastasis, the effect of axillary lymph node dissection (ALND) is controversial. The purpose of this study is to compare the safety and efficacy of sentinel lymph node biopsy (SLNB) alone versus ALND in patients with early breast cancer and sentinel node metastasis. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library databases from 1965 to February 2014. All data were analyzed using Review Manager Software 5.2. RESULTS: 12 studies, which included 130,575 patients from five randomized controlled trials and seven observational studies, met our inclusion criteria. 26,870 early breast cancer patients underwent SLNB alone and 103,705 underwent ALND. Patients underwent ALND had more paresthesia (risk ratio [RR] 0.26, 95% confidence interval [CI] 0.20-0.33; p < 0.01) and lymphedema (RR 0.28, 95% CI 0.20-0.41; p < 0.01) than those had SLNB alone. There were no significant differences in overall survival (hazard ratio [HR] 0.95, 95% CI 0.85-1.06; p = 0.35), disease-free survival (HR 1.00, 95% CI 0.98-1.02, p = 0.96), and locoregional recurrence (RR 0.92, 95% CI 0.59-1.44; p = 0.73). CONCLUSION: Current evidence indicates that axillary dissection may be omitted in early breast cancer patients with sentinel lymph metastasis.


Subject(s)
Breast Neoplasms/secondary , Early Diagnosis , Lymph Node Excision/methods , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy/methods , Axilla , Breast Neoplasms/diagnosis , Female , Humans , Lymph Nodes/surgery , Lymphatic Metastasis
20.
Invest Ophthalmol Vis Sci ; 42(5): 1119-24, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11274094

ABSTRACT

PURPOSE: To investigate the effects of age on transient vernier visual evoked potential (VEP) and vernier acuity estimated by extrapolation. METHODS: Transient vernier VEPs were examined in normal subjects aged 20 to 75 years. Vernier offsets were presented for the first 350 msec of the stimulus period, and the segments were then realigned in the following 400 msec. The six vernier offsets used were 20, 40, 60, 80, 100, and 140 seconds of arc. Averaging for each offset setting produced vernier VEP waveforms, for which amplitude and latency of visual evoked response and background electroencephalographic (EEG) noise level were determined. Extrapolation of the function relating signal-to-noise ratio and log vernier offset to a ratio of 1.0 resulted in an estimate of vernier acuity. RESULTS: Amplitude of vernier VEP waveforms was significantly reduced in subjects more than 60 years of age, and the latency to the first negative peak was progressively prolonged with increasing age. There was no statistically significant change in electroencephalographic (EEG) noise with advancing age. VEP vernier acuity was significantly degraded in the 61- to 75-year age group. These results are parallel to recent psychophysical findings that alignment performance is worse in older persons than in younger ones. CONCLUSIONS: The present findings provide the first electrophysiological evidence of age-related cortical degeneration associated with vernier processing. Reduced neural activity probably contributes to the loss of vernier acuity with advancing age. Also provided are the first normative data for subjects of different ages for vernier VEP and VEP vernier acuity. Moreover, the present study has demonstrated that vernier VEP is sensitive to neural changes and therefore may be applied in clinical situations to evaluate the integrity of the visual system.


Subject(s)
Aging/physiology , Evoked Potentials, Visual/physiology , Visual Cortex/physiology , Adult , Aged , Electroencephalography , Female , Humans , Male , Middle Aged , Visual Acuity
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