Bovine STAT5A gene polymorphism and its influence on growth traits in Podolica breed

2016 ◽  
Vol 56 (7) ◽  
pp. 1056 ◽  
Author(s):  
Maria Selvaggi ◽  
Angela Gabriella D'Alessandro ◽  
Cataldo Dario
Keyword(s):  
Target Genes ◽  
Bos Taurus ◽  
Growth Traits ◽  
Target Cells ◽  
Signal Transducers ◽  
Biological Adaptation ◽  
Genotype Frequencies ◽  
Growth Hormone Action ◽  
Long Time ◽  
Stat5a Gene

Signal transducers and activators of transcription (STAT) are latent cytoplasmic transcription factors that mediate the actions of a variety of peptide hormones and cytokines within target cells. STAT5A is the main mediator of growth hormone action on target genes and plays a key role as intracellular mediator of prolactin signalling. In this study, the T→C nucleotide polymorphism at position 12 743 in exon 16 of the bovine STAT5A gene was investigated with polymerase chain reaction-restriction fragment length polymorphism in a sample of Podolica young bulls. The Podolica breed derives from Bos primigenius podolicus (forebears of the modern Bos taurus), it has been present in Italy for a very long time and represents yet another example of successful biological adaptation to a hostile environment. The aims of this study were to estimate the allele and genotype frequencies in Podolica breed and to investigate a possible relationship between this polymorphism and some growth performance traits. The observed frequencies of C and T alleles were 0.344 and 0.656, respectively. The TT genotype was the most frequent in the studied population followed by TC and CC ones. Moreover, the animals carrying TT genotypes seem to show an initial faster growth, which determined higher bodyweight at 90 and 270 days of age; conversely, CC individuals exhibit a faster growth in the post-weaning period achieving the higher bodyweight at 450 days of age.

Vitamin D

2005 ◽  
Vol 289 (1) ◽  
pp. F8-F28 ◽  
Author(s):  
Adriana S. Dusso ◽  
Alex J. Brown ◽  
Eduardo Slatopolsky
Keyword(s):  
Vitamin D ◽  
Target Genes ◽  
Endocrine System ◽  
Target Cells ◽  
Vitamin D Metabolism ◽  
Diverse Range ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Single Receptor ◽  
Recent Developments

The vitamin D endocrine system plays an essential role in calcium homeostasis and bone metabolism, but research during the past two decades has revealed a diverse range of biological actions that include induction of cell differentiation, inhibition of cell growth, immunomodulation, and control of other hormonal systems. Vitamin D itself is a prohormone that is metabolically converted to the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)2D]. This vitamin D hormone activates its cellular receptor (vitamin D receptor or VDR), which alters the transcription rates of target genes responsible for the biological responses. This review focuses on several recent developments that extend our understanding of the complexities of vitamin D metabolism and actions: the final step in the activation of vitamin D, conversion of 25-hydroxyvitamin D to 1,25(OH)2D in renal proximal tubules, is now known to involve facilitated uptake and intracellular delivery of the precursor to 1α-hydroxylase. Emerging evidence using mice lacking the VDR and/or 1α-hydroxylase indicates both 1,25(OH)2D3-dependent and -independent actions of the VDR as well as VDR-dependent and -independent actions of 1,25(OH)2D3. Thus the vitamin D system may involve more than a single receptor and ligand. The presence of 1α-hydroxylase in many target cells indicates autocrine/paracrine functions for 1,25(OH)2D3in the control of cell proliferation and differentiation. This local production of 1,25(OH)2D3is dependent on circulating precursor levels, providing a potential explanation for the association of vitamin D deficiency with various cancers and autoimmune diseases.

scholarly journals Triptolide Modulates the Expression of Inflammation-Associated lncRNA-PACER and lincRNA-p21 in Mycobacterium tuberculosis–Infected Monocyte-Derived Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ousman Tamgue ◽  
Julius Ebua Chia ◽  
Frank Brombacher
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Target Genes ◽  
Cell Function ◽  
Immune Cell ◽  
Biological Activities ◽  
Target Cells ◽  
Dependent Manner ◽  
Direct Targeting ◽  
Non Coding Rnas ◽  
Alamarblue Assay

Triptolide is a diterpene triepoxide, which performs its biological activities via mechanisms including induction of apoptosis, targeting of pro-inflammatory cytokines, and reshaping of the epigenetic landscape of target cells. However, the targeting of long non-coding RNAs (lncRNAs) by triptolide has not yet been investigated, despite their emerging roles as key epigenetic regulators of inflammation and immune cell function during Mycobacterium tuberculosis (Mtb) infection. Hence, we investigated whether triptolide targets inflammation-associated lncRNA-PACER and lincRNA-p21 and how this targeting associates with Mtb killing within monocyte-derived macrophages (MDMs).Using RT-qPCR, we found that triptolide induced the expression of lincRNA-p21 but inhibited the expression of lncRNA-PACER in resting MDMs in a dose- and time-dependent manner. Moreover, Mtb infection induced the expression of lincRNA-p21 and lncRNA-PACER, and exposure to triptolide before or after Mtb infection led to further increase of Mtb-induced expression of these lncRNAs in MDMs. We further found that contrary to lncRNA-PACER, triptolide time- and dose-dependently upregulated Ptgs-2, which is a proximal gene regulated by lncRNA-PACER. Also, low-concentration triptolide inhibited the expression of cytokine IL-6, a known target of lincRNA-p21. Mtb infection induced the expression of IL-6 and Ptgs-2, and triptolide treatment further increased IL-6 but decreased Ptgs-2 expression in Mtb-infected MDMs. The inverse relation between the expression of these lncRNAs and their target genes is concordant with the conception that these lncRNAs mediate, at least partially, the cytotoxic and/or anti-inflammatory activities of triptolide in both resting and activated MDMs. Using the CFU count method, we found that triptolide decreased the intracellular growth of Mtb HN878. The alamarBlue assay showed that this decreased Mtb HN878 growth was not as a result of direct targeting of Mtb HN878 by triptolide, but rather evoking MDMs’ intracellular killing mechanisms which we speculate could include triptolide-induced enhancement of MDMs’ effector killing functions mediated by lncRNA-PACER and lincRNA-p21. Altogether, these results provide proof of the modulation of lncRNA-PACER and lincRNA-p21 expression by triptolide, and a possible link between these lncRNAs, the enhancement of MDMs’ effector killing functions and the intracellular Mtb-killing activities of triptolide. These findings prompt for further investigation of the precise contribution of these lncRNAs to triptolide-induced activities in MDMs.

scholarly journals Efficient genome editing in primary cells and in vivo using viral-derived “Nanoblades” loaded with Cas9/sgRNA ribonucleoproteins

2017 ◽  
Author(s):  
Philippe E. Mangeot ◽  
Valérie Risson ◽  
Floriane Fusil ◽  
Aline Marnef ◽  
Emilie Laurent ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genome Editing ◽  
Target Genes ◽  
Bone Marrow Cells ◽  
Leukemia Virus ◽  
Target Cells ◽  
Mouse Bone Marrow ◽  
Primary Cells ◽  
Hematopoietic Stem

AbstractProgrammable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells and living organisms. However, their delivery into target cells can be technically challenging when working with primary cells or in vivo. Using engineered murine leukemia virus-like particles loaded with Cas9/sgRNA ribonucleoproteins (“Nanoblades”), we were able to induce efficient genome-editing in cell lines and primary cells including human induced pluripotent stem cells, human hematopoietic stem cells and mouse bone-marrow cells. Transgene-free Nanoblades were also capable of in vivo genome-editing in mouse embryos and in the liver of injected mice. Nanoblades can be complexed with donor DNA for “all-in-one” homology-directed repair or programmed with modified Cas9 variants to mediate transcriptional up-regulation of target genes. Nanoblades preparation process is simple, relatively inexpensive and can be easily implemented in any laboratory equipped for cellular biology.

scholarly journals Identification of MC4R gene and its association with body weight and body size in Kebumen Ongole Grade cattle

2018 ◽  
Vol 43 (2) ◽  
pp. 87
Author(s):  
D. Maharani ◽  
A. Fathoni ◽  
S. Sumadi ◽  
T. Hartatik ◽  
M. Khusnudin
Keyword(s):  
Body Length ◽  
Growth Traits ◽  
Average Daily Gain ◽  
Pcr Amplification ◽  
Growth Trait ◽  
Chest Circumference ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Mc4r Gene ◽  
Genotype Frequencies

MC4R gene is known as an important candidate gene for the growth trait. The purpose of this research was to identify the MC4R gene in Kebumen Ongole grade cattle and examine its association with growth traits. Data of birth weight (BW), weaning weight (WW), birth body length (BBL), birth chest circumference (BCC), birth shoulder height (BSH), weaning body length (WBL), weaning chest circumference(WCC), weaning shoulder height (WSH) and average daily gain (ADG) were collected and used for analysis of MC4R gene. Sixty blood samples were collected for DNA isolation and PCR amplification. The single nucleotide polymorphisms (SNP) g.1133 C>G was used for genotyping by using PCR-RFLP methods. The frequenciy of G allele (0.59) was greater than C allele (0.41). The highest genotype frequencies have been detected in CG heterozygote animals (0.52) followed by GG (0.33) and CC (0.15) in homozygote animals. The results of Pearson ‘s Chi-square test indicated that the population was not deviate (P>0.05) from the Hardy-Weinberg equilibrium (HWE). The SNP g. 1133 C>G of MC4R gene indicated affecting high birth body length with GG genotype (P<0.05). In conclusion, the SNP g. 1133 C>G may can be a marker for birth body length of calf selection.

Growth Traits and Composition of Two- and Three-Way-Cross Intact Male Progeny of Bos Taurus and Bos Indicus × Bos Taurus Dams

1987 ◽  
Vol 65 (1) ◽  
pp. 16-32 ◽  
Author(s):  
Karen M. Van Ornum ◽  
Curtiss M. Bailey ◽  
Thomas P. Ringkob ◽  
Young O. Koh
Keyword(s):  
Bos Taurus ◽  
Growth Traits ◽  
Bos Indicus ◽  
Intact Male ◽  
Male Progeny

117 Subclinical Mastitis Reduces Ovulation and Oocyte Quality in Milk-Producing Cows

2018 ◽  
Vol 30 (1) ◽  
pp. 198
Author(s):  
G. Santos ◽  
M. P. Bottino ◽  
M. B. D. Ferreira ◽  
J. C. Silveira ◽  
A. C. F. C. M. Avila ◽  
...  
Keyword(s):  
Follicular Fluid ◽  
Target Genes ◽  
Bos Taurus ◽  
Bos Indicus ◽  
Cumulus Cell ◽  
Cumulus Cells ◽  
Subclinical Mastitis ◽  
Oocyte Quality ◽  
Ovulation Rate ◽  
Follicular Dynamics

The aim was to evaluate the effect of subclinical mastitis by somatic cell count (SCC) on follicular dynamics, ovulation, oocyte and cumulus cell quality, exosome size and concentration in milk-producing cows. Crossbred cows (Bos taurus × Bos indicus; that is, Holstein × Gyr) were randomly allocated to control (SCC <200,000 cells mL−1] and mastitis (SCC >400,000 cells mL−1) groups. In experiment 1 (follicular dynamics), cows (n = 57) were submitted to ultrasonographic evaluations every 24 h, after removal of an intravaginal progesterone device (Day 8) up to Day 10. From Day 10, ultrasound evaluations were performed every 12 h, until ovulation or until 96 h after progesterone device withdrawal, in order to follow final dominant follicle growth and ovulation. In experiment 2 (oocyte, cumulus cells, and follicular fluid evaluation), cows (n = 23) were submitted to follicular aspirations, preceded by synchronization of the emergence of the follicular wave. The levels of target genes in cumulus cells (BCL2, BAX, PI3K, PTEN, FOXO3) were evaluated by RT-qPCR. In the follicular fluid, the exosomes were isolated for evaluation of particle size. Data were analysed by the Glimmix procedure of SAS (SAS Institute Inc., Cary, NC, USA). Ovulation rate (P = 0.09) was higher in control cows [control 77.42% (24/31) and mastitis 57.69% (15/26)]. Viable oocyte rate (P = 0.01) was also higher in control cows [control 59.1% (130/220) and mastitis 41.9% (125/298)]. The dynamics of follicular growth did not differ between groups. The number of degenerate oocytes (P = 0.001) was higher in cows of the mastitis group. In the evaluation of cumulus cell gene expression, there was a higher abundance of BAX transcripts (P = 0.003) in cells of mastitis cows. Additionally, the mean and mode of exosome diameter in mastitis cows were smaller (P = 0.03 and P = 0.02, respectively). In conclusion, ovulation rate, oocyte quality, and follicular fluid exosome diameter were lower in cows with subclinical mastitis, demonstrating a link between mammary gland sanitary status and reproduction.

scholarly journals Small Extracellular Vesicles from Human Fetal Dermal Cells and Their MicroRNA Cargo: KEGG Signaling Pathways Associated with Angiogenesis and Wound Healing

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Cinzia Maria Chinnici ◽  
Giandomenico Amico ◽  
Alessia Gallo ◽  
Gioacchin Iannolo ◽  
Nicola Cuscino ◽  
...  
Keyword(s):  
Wound Healing ◽  
Signaling Pathways ◽  
Extracellular Vesicles ◽  
Target Genes ◽  
Fold Increase ◽  
Target Cells ◽  
Published Data ◽  
Dermal Cell ◽  
Thrombospondin 1

The use of cell secreted factors in clinical settings could be an alternative to conventional cell therapy, with the advantage of limiting concerns generally associated with traditional cell transplantation, such as tumorigenicity, immunoreactivity, and carrying of infections. Based on our published data, we predict a potential role for extracellular vesicles (EVs) in contributing to the proangiogenic activity of human fetal dermal cell secretome. Depletion of nanosized EVs from secretome significantly impaired its ability to induce formation of mesh-like structures in vitro. The isolated EVs were characterized for size and concentration by nanoparticle tracking analysis, and for protein markers (Rab5+, Alix+, CD63+, and calnexin-). The microRNA profile of EVs revealed 87 microRNAs significantly upregulated (≥15-fold increase) in fetal compared to adult dermal cell-derived EVs. Interestingly, these upregulated microRNAs included microRNAs with a validated role in angiogenesis according to literature. Moreover, the DIANA-TarBase v7.0 analysis confirmed enrichment in the KEGG signaling pathways associated with angiogenesis and wound healing, with the identification of putative target genes including thrombospondin 1. To validate the in silico data, EVs were also characterized for total protein contents. When tested in in vitro angiogenesis, fetal dermal cell-derived EVs were more effective than their adult counterpart in inducing formation of complete mesh-like structures. Furthermore, treatment of fibroblasts with fetal dermal-derived EVs determined a 4-fold increase of thrombospondin 1 protein amounts compared with the untreated fibroblasts. Finally, visualization of CSFE-labeled EVs in the cytosol of target cells suggested a successful uptake of these particles at 4-8 hours of incubation. We conclude that EVs are important contributors of the proangiogenic effect of fetal dermal cell secretome. Hence, EVs could also serve as vehicle for a successful delivery of microRNAs or other molecules of therapeutic interest to target cells.

scholarly journals Fibronectin on the Surface of Myeloma Cell-derived Exosomes Mediates Exosome-Cell Interactions

2015 ◽  
Vol 291 (4) ◽  
pp. 1652-1663 ◽  
Author(s):  
Anurag Purushothaman ◽  
Shyam Kumar Bandari ◽  
Jian Liu ◽  
James A. Mobley ◽  
Elizabeth E. Brown ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Target Cell ◽  
Target Genes ◽  
Cell Interaction ◽  
Myeloma Cell ◽  
Cell Interactions ◽  
Target Cells ◽  
Heparin Binding ◽  
Downstream Target ◽  
Tumor Microenvironments

Exosomes regulate cell behavior by binding to and delivering their cargo to target cells; however, the mechanisms mediating exosome-cell interactions are poorly understood. Heparan sulfates on target cell surfaces can act as receptors for exosome uptake, but the ligand for heparan sulfate on exosomes has not been identified. Using exosomes isolated from myeloma cell lines and from myeloma patients, we identify exosomal fibronectin as a key heparan sulfate-binding ligand and mediator of exosome-cell interactions. We discovered that heparan sulfate plays a dual role in exosome-cell interaction; heparan sulfate on exosomes captures fibronectin, and on target cells it acts as a receptor for fibronectin. Removal of heparan sulfate from the exosome surface releases fibronectin and dramatically inhibits exosome-target cell interaction. Antibody specific for the Hep-II heparin-binding domain of fibronectin blocks exosome interaction with tumor cells or with marrow stromal cells. Regarding exosome function, fibronectin-mediated binding of exosomes to myeloma cells activated p38 and pERK signaling and expression of downstream target genes DKK1 and MMP-9, two molecules that promote myeloma progression. Antibody against fibronectin inhibited the ability of myeloma-derived exosomes to stimulate endothelial cell invasion. Heparin or heparin mimetics including Roneparstat, a modified heparin in phase I trials in myeloma patients, significantly inhibited exosome-cell interactions. These studies provide the first evidence that fibronectin binding to heparan sulfate mediates exosome-cell interactions, revealing a fundamental mechanism important for exosome-mediated cross-talk within tumor microenvironments. Moreover, these results imply that therapeutic disruption of fibronectin-heparan sulfate interactions will negatively impact myeloma tumor growth and progression.

SUMO-1 conjugation selectively modulates STAT1-mediated gene responses

Blood ◽  
2005 ◽  
Vol 106 (1) ◽  
pp. 224-226 ◽  
Author(s):  
Daniela Ungureanu ◽  
Sari Vanhatupa ◽  
Juha Grönholm ◽  
Jorma J. Palvimo ◽  
Olli Silvennoinen
Keyword(s):  
Target Genes ◽  
Attachment Site ◽  
Binding Activity ◽  
Signal Transducers ◽  
Dna Binding Activity ◽  
Interferon Regulatory Factor 1 ◽  
Defective Mutant ◽  
Physiologic Function ◽  
Ifn Γ ◽  
Ligase Function

Signal transducers and activators of transcription 1 (STAT1) is a critical mediator of interferon (IFN)–induced gene responses. Recently, STAT1 was found to become modified by small ubiquitin-like modifier 1 (SUMO-1) conjugation at Lys703 through the SUMO E3 ligase function of protein inhibitors of activated STAT (PIAS) proteins. However, the physiologic function of sumoylation in STAT1 is still unclear. Here, we show that mutations in the SUMO attachment site in STAT1 result in increased transcriptional activity in a fashion that is selective among IFN-γ target genes. The sumoylation-defective STAT1 mutant displayed increased induction of guanylate-binding protein 1 (GBP1) and transporters associated with antigen presentation 1 (TAP1) transcription but not interferon regulatory factor 1 (IRF1) transcription. Moreover, the sumoylation-defective mutant STAT1-KR showed a prolonged DNA-binding activity and nuclear localization in response to IFN-γ stimulation. These results suggest that sumoylation has a defined negative regulatory effect on selective STAT1-mediated transcription responses.

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