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1.
Domest Anim Endocrinol ; 82: 106766, 2023 01.
Article in English | MEDLINE | ID: mdl-36182815

ABSTRACT

The relation between circulating concentrations of progesterone and 17ß-estradiol prior to insemination play a key role in optimizing fertility in cattle. This study aimed to determine the impact of endogenous progesterone (P4) and estradiol (E2) concentrations on uterine bacterial community abundance and diversity in beef cattle. Angus-influenced heifers were subjected to an industry standard estrous synchronization protocol. Uterine flushes were collected on d -2 (endogenous P4) and d 0 (endogenous E2) and used for targeting the V4 hypervariable region of 16S rRNA bacterial gene. Plasma was collected on d -2 and 0 for quantification of P4 and E2 concentrations by radioimmunoassay, respectively. Heifers were allotted to one of the following groups: High P4 + High E2 (H-H; n = 11), High P4 + Low E2 (H-L; n = 9), Low P4 + High E2 (L-H; n = 9), Low P4 + Low E2 (L-L; n = 11). Results indicated that Shannon's diversity index tended to be greater for H-L heifers compared to L-H heifers on d 0 (P = 0.10). For H-L heifers from d -2 to d 0, the relative abundance of Actinobacteria decreased and Tenericutes increased (P < 0.01). Within phylum Actinobacteria, the relative abundance of Corynebacterium decreased from d -2 to d 0 in treatment groups H-H, H-L, and L-L (P < 0.05); however, did not differ by d for L-H heifers. Within phylum Tenericutes, the relative abundance of Ureaplasma increased from d -2 to d 0 for H-L heifers (P = 0.01). Additionally for H-L heifers, the relative abundance of Bacteroidetes tended to increase from day -2 to on d 0 (P = 0.07). For H-L heifers, uterine pH increased from day -2 to d 0 (P = 0.05). These results suggest that differing endogenous concentrations of P4 and E2 may be associated with shifts in uterine microbiota and pH, and this could ultimately impact fertility outcomes in beef cattle.


Subject(s)
Estrus Synchronization , Progesterone , Cattle , Female , Animals , Estrus Synchronization/methods , RNA, Ribosomal, 16S/genetics , Estradiol , Estrus , Insemination, Artificial/veterinary
2.
Oncogene ; 36(22): 3137-3148, 2017 06 01.
Article in English | MEDLINE | ID: mdl-27941877

ABSTRACT

A well-studied RNA-binding protein Hu Antigen-R (HuR), controls post-transcriptional gene regulation and undergoes stress-activated caspase-3 dependent cleavage in cancer cells. The cleavage products of HuR are known to promote cell death; however, the underlying molecular mechanisms facilitating caspase-3 activation and HuR cleavage remains unknown. Here, we show that HuR cleavage associated with active caspase-3 in oral cancer cells treated with ionizing radiation and chemotherapeutic drug, paclitaxel. We determined that oral cancer cells overexpressing cyclooxygenase-2 (COX-2) limited the cleavage of caspase-3 and HuR, which reduced the rate of cell death in paclitaxel resistant oral cancer cells. Specific inhibition of COX-2 by celecoxib, promoted apoptosis through activation of caspase-3 and cleavage of HuR in paclitaxel-resistant oral cancer cells, both in vitro and in vivo. In addition, oral cancer cells overexpressing cellular HuR increased the half-life of COX-2 mRNA, promoted COX-2 protein expression and exhibited enhanced tumor growth in vivo in comparison with cells expressing a cleavable form of HuR. Finally, our ribonucleoprotein immunoprecipitation and sequencing (RIP-seq) analyses of HuR in oral cancer cells treated with ionizing radiation (IR), determined that HuR cleavage product-1 (HuR-CP1) bound and promoted the expression of mRNAs encoding proteins involved in apoptosis. Our results indicated that, cellular non-cleavable HuR controls COX-2 mRNA expression and enzymatic activity. In addition, overexpressed COX-2 protein repressed the cleavage of caspase-3 and HuR to promote drug resistance and tumor growth. Altogether, our observations support the use of the COX-2 inhibitor celecoxib, in combination with paclitaxel, for the management of paclitaxel resistant oral cancer cells.


Subject(s)
Carcinoma, Squamous Cell/genetics , Caspase 3/metabolism , Cyclooxygenase 2/genetics , Mouth Neoplasms/genetics , RNA-Binding Proteins/metabolism , Carcinoma, Squamous Cell/pathology , Humans , Mouth Neoplasms/pathology
3.
J Dent Res ; 91(7): 651-8, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22302144

ABSTRACT

Cytokines are critical mediators of inflammation and host defenses. Regulation of cytokines can occur at various stages of gene expression, including transcription, mRNA export, and post- transcriptional and translational levels. Among these modes of regulation, post-transcriptional regulation has been shown to play a vital role in controlling the expression of cytokines by modulating mRNA stability. The stability of cytokine mRNAs, including TNFα, IL-6, and IL-8, has been reported to be altered by the presence of AU-rich elements (AREs) located in the 3'-untranslated regions (3'UTRs) of the mRNAs. Numerous RNA-binding proteins and microRNAs bind to these 3'UTRs to regulate the stability and/or translation of the mRNAs. Thus, this paper describes the cooperative function between RNA-binding proteins and miRNAs and how they regulate AU-rich elements containing cytokine mRNA stability/degradation and translation. These mRNA control mechanisms can potentially influence inflammation as it relates to oral biology, including periodontal diseases and oral pharyngeal cancer progression.


Subject(s)
Cytokines/genetics , Gene Expression Regulation , MicroRNAs/metabolism , RNA, Messenger/genetics , RNA-Binding Proteins/metabolism , 3' Untranslated Regions/genetics , Base Sequence , Cyclooxygenase 2/biosynthesis , Cyclooxygenase 2/genetics , Cytokines/biosynthesis , Inflammation/genetics , Interleukin-6/biosynthesis , Interleukin-6/genetics , Interleukin-8/biosynthesis , Interleukin-8/genetics , Molecular Sequence Data , RNA Processing, Post-Transcriptional/genetics , RNA Stability/genetics , RNA, Messenger/biosynthesis , Regulatory Sequences, Ribonucleic Acid/genetics , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/genetics , Vascular Endothelial Growth Factor A/biosynthesis , Vascular Endothelial Growth Factor A/genetics
4.
J Dent Res ; 87(8): 772-6, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18650551

ABSTRACT

Human saliva contains thousands of mRNAs, some of which have translational value as diagnostic markers for human diseases. We have found that more than 30% of the mRNAs detected in human saliva contain AU-rich elements (ARE) in their 3' untranslated regions (3'UTR). Since AREs are known to contribute to RNA turnover by forming complexes with ARE-binding proteins, we hypothesized that salivary mRNA stability is mediated by ARE-binding proteins in human saliva. To test this hypothesis, we monitored the in vitro degradation of a radiolabeled ARE-containing salivary mRNA (IL-8) in salivary protein extracts. The degradation of IL-8 mRNA was accelerated by competition for saliva ARE-binding proteins through the addition of excess unlabeled IL-8 mRNA fragments containing 4 tandem AREs. UV cross-linking and immunoprecipitation experiments revealed 2 ARE-binding proteins, AUF1 and HuR, associated with IL-8 mRNA in saliva. These results demonstrate that ARE-binding proteins contribute to the stability of ARE mRNAs in human saliva.


Subject(s)
Antigens, Surface/metabolism , Heterogeneous-Nuclear Ribonucleoprotein D/metabolism , RNA Stability/physiology , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , Saliva/metabolism , ELAV Proteins , ELAV-Like Protein 1 , Heterogeneous Nuclear Ribonucleoprotein D0 , Humans , Interleukin-8/genetics , Interleukin-8/metabolism , Reference Values
5.
ISA Trans ; 47(2): 179-88, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18093589

ABSTRACT

Safe operating environment is essential for all complex industrial processes. The safety issues in steel rolling mill when the hot strip passes through consecutive mill stands have been considered in this paper. Formation of sag in strip is a common problem in the rolling process. The excessive sag can lead to scrap runs and damage to machinery. Conventional controllers for mill actuation system are based on a rolling model. The factors like rise in temperature, aging, wear and tear are not taken into account while designing a conventional controller. Therefore, the conventional controller cannot yield a requisite controlled output. In this paper, a new Genetic-neuro-fuzzy hybrid controller without tension sensor has been proposed to optimize the quantum of excessive sag and reduce it. The performance of the proposed controller has been compared with the performance of fuzzy logic controller, Neuro-fuzzy controller and conventional controller with the help of data collected from the plant. The simulation results depict that the proposed controller has superior performance than the other controllers.

6.
Biorheology ; 27(5): 619-30, 1990.
Article in English | MEDLINE | ID: mdl-2271756

ABSTRACT

Pulsatile flow of a Casson fluid under the influence of a periodic body acceleration has been studied in this paper. An implicit finite difference numerical procedure has been used to analyze the flow. Applicability of this method has been checked by comparing the obtained results with the analytical solution for Newtonian flow and explicit scheme solution. The agreement between the implicit and explicit scheme solutions and the analytical solution is good (error less than 1%). Flow variables have been computed at three locations in cardiovascular system (wide (femoral) and narrow (arteriole and coronary) tubes). Effects of yield stress, tube radius and pressure gradient combined, body acceleration amplitude and frequency etc., on flow have been studied. The following observations have been made: (i) Initial transient time It changes with yield stress in narrow tubes are insignificant, whereas in wide tubes It decreases with yield stress; (ii) The axial velocity and fluid acceleration variations with yield stress are uniform (changes only quantitatively, profiles shape remain same) in narrow tubes, whereas in wide tubes these variations are non-uniform (profiles change qualitatively as well as quantitatively); (iii) Yield stress effects on wall shear amplitude are insignificant in narrow tubes (congruent to 0.3% in arteriole and congruent to 6% in femoral); and (iv) For Newtonian fluid, mean flow rate does not change with body acceleration amplitude a0 and frequency fb but it increases (decreases) with a0(fb) for Casson fluid.


Subject(s)
Acceleration/adverse effects , Models, Biological , Pulsatile Flow/physiology , Regional Blood Flow/physiology , Cardiovascular Physiological Phenomena , Humans , Mathematics , Time Factors
7.
Biorheology ; 27(5): 747-58, 1990.
Article in English | MEDLINE | ID: mdl-2271765

ABSTRACT

A mathematical model has been proposed to study the pulsatile flow of a power-law fluid through rigid circular tubes under the influence of a periodic body acceleration. Numerical solutions have been obtained by using finite difference method. The accuracy of the numerical procedure has been checked by comparing the obtained numerical results with other numerical and analytical solutions. It is found that the agreement between them is quite good. Interaction of non-Newtonian nature of fluid with the body acceleration has been investigated by using the physiological data for two particular cases (coronary and femoral arteries). The axial velocity, fluid acceleration, wall shear stress and instantaneous volume flow rate have been computed and their variations with different parameters have been analyzed. The following important observations have been made: (i) The velocity and acceleration profiles can have more than one maxima, this is in contrast with usual parabolic profiles where they have only one maximum at the axis. As n increases, the maxima shift towards the axis; (ii) For the flow with no body acceleration, the amplitude of both, wall shear and flow rate, increases with n, whereas for the flow with body acceleration, the amplitude of wall shear (flow rate) increases (decreases) as n increases; (iii) In the absence of body acceleration, pseudoplastic (dilatant) fluids, with low frequency pulsations, have higher (lower) value of maximum flow rate Qmax than Newtonian fluids, whereas for high frequencies, opposite behavior has been observed; for flow with body acceleration pulsations gives higher (lower) value of Qmax for pseudoplastic (dilatant) fluids than Newtonian fluids.


Subject(s)
Acceleration , Blood Physiological Phenomena , Models, Biological , Pulsatile Flow , Blood Flow Velocity , Coronary Circulation , Femoral Artery , Mathematics , Regional Blood Flow , Stress, Mechanical
8.
Biorheology ; 26(4): 835-46, 1989.
Article in English | MEDLINE | ID: mdl-2611375

ABSTRACT

The effects of polar nature of blood and pulsatility on flow through a stenosed tube have been analysed by assuming blood as a micropolar fluid. Linearized solutions of basic equations are obtained through consecutive applications of finite Hankel and Laplace transforms. The analytical expressions for axial and particle angular velocities, wall shear stress, resistance to flow and apparent viscosity have been obtained. The axial velocity profiles for Newtonian and micropolar fluids have been compared. The interesting observation of this analysis is velocity, in certain parts of cycle, for micropolar fluid is higher than Newtonain fluid. Variation of apparent viscosity eta a with tube radius shows both inverse Fahraeus-Lindqvist and Fahraeus-Lindqvist effects. Finally, the resistance to flow and wall shear stress for normal and diseased blood have been computed and compared.


Subject(s)
Arterial Occlusive Diseases/physiopathology , Blood Circulation/physiology , Blood Flow Velocity/physiology , Blood Viscosity , Constriction, Pathologic/physiopathology , Humans , Mathematics , Models, Cardiovascular , Pulsatile Flow , Rheology
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