1,127 research outputs found
Outcome of patients with splanchnic venous thrombosis presenting without overt MPN: a role for the JAK2 V617F mutation re-evaluation.
No full textThe Ability of Cyanobacterial Cells to Restore UV-B Radiation Induced Damage to Photosystem II is Influenced by Photolyase Dependent DNA Repair
No full textDamage of DNA and Photosystem-II are among the most significant effects of UV-B irradiation in photosynthetic organisms. Both damaged DNA and Photosystem-II can be repaired, which represent important defense mechanisms against detrimental UV-B effects. Correlation of Photosystem-II damage and repair with the concurrent DNA damage and repair was investigated in the cyanobacterium Synechocystis PCC6803 using its wild type and a photolyase deficient mutant, which is unable to repair UV-B induced DNA damages. A significant amount of damaged DNA accumulated during UV-B exposure in the photolyase mutant concomitant with decreased Photosystem-II activity and D1 protein amount. The transcript level of psbA3, which is a UV-responsive copy of the psbA gene family encoding the D1 subunit of the Photosystem-II reaction center, is also decreased in the photolyase mutant. The wild-type cells, however, did not accumulate damaged DNA during UV-B exposure, suffered smaller losses of Photosystem-II activity and D1 protein, and maintained higher level of psbA3 transcripts than the photolyase mutant. It is concluded that the repair capacity of Photosystem-II depends on the ability of cells to repair UV-B-damaged DNA through maintaining the transcription of genes, which are essential for protein synthesis-dependent repair of the Photosystem-II reaction center
Cyclin D1 immunohistochemical expression and somatic mutations in canine oral melanoma
No full textCanine oral melanoma (COM) is the most frequent tumour with oral localization in dogs. Copy number gains and amplifications of CCND1, a gene coding for Cyclin D1, are the most frequent chromosomal aberrations described in human non-UV induced melanomas. Twenty-eight cases of COM were retrieved from paraffin-blocks archives. A total of 4 μm thick sections were immunostained with an antibody against human Cyclin D1 and Ki-67. Cyclin D1 and Ki-67 expressions were scored through two counting methods. DNA was extracted from 20 μm thick sections of formalin-fixed paraffin-embedded blocks. Pathological and surrounding healthy tissue was extracted independently. Cyclin D1 immunolabelling was detected in 69% (18/26) while Ki-67 was present in 88.5% (23/26) of cases. Statistical analysis revealed correlation between two counting methods for Cyclin D1 (r = 0.54; P = .004) and Ki-67 (r = 0.56; P = .003). The correlation found between Ki-67 and Cyclin D1 indexes in 16/26 cases labelled by both antibodies (r = 0.7947; P = .0002) suggests a possible use of Cyclin D1 index as prognostic marker. Polymerase chain reaction analysis on CCND1 coding sequence revealed the presence of nine somatic mutations in seven samples producing synonymous, missense and stop codons. Since none of the single-nucleotide polymorphisms was found to be recurrent, it is suggested that overexpression of Cyclin D1 may be the consequence of alterations of CCND1 upstream regions or other genetic aberrations not detectable with the methodology used in this study. Future studies are needed to verify the potential use of Cyclin D1 index as prognostic indicator and to highlight the molecular events responsible for Cyclin D1 overexpression in COMs
MiR-34a Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells via the RBP2/NOTCH1/CYCLIN D1 Coregulatory Network
No full textSummaryMiR-34a was demonstrated to be upregulated during the osteogenic differentiation of human adipose-derived stem cells (hASCs). Overexpression of miR-34a significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of osteogenesis-associated genes in hASCs in vitro. Enhanced heterotopic bone formation in vivo was also observed upon overexpression of miR-34a in hASCs. Mechanistic investigations revealed that miR-34a inhibited the expression of retinoblastoma binding protein 2 (RBP2) and reduced the luciferase activity of reporter gene construct comprising putative miR-34a binding sites in the 3′ UTR of RBP2. Moreover, miR-34a downregulated the expression of NOTCH1 and CYCLIN D1 and upregulated the expression of RUNX2 by targeting RBP2, NOTCH1, and CYCLIN D1. Taken together, our results suggested that miR-34a promotes the osteogenic differentiation of hASCs via the RBP2/NOTCH1/CYCLIN D1 coregulatory network, indicating that miR-34a-targeted therapy could be a valuable approach to promote bone regeneration
The ability of a D1/D2 antagonist combination to antagonize the discriminative stimulus properties of cocaine
No full textWhereas dopamine reuptake inhibitors substitute for the discriminative stimulus properties of cocaine, neither norepinepherine nor serotonin reuptake inhibitors generally do (Kleven, Anthony & Woolverton, 1990), suggesting that the dopamine system mediates cocaine's stimulus properties. Interestingly, selective D1 and D2 agonists do not substitute completely for the cocaine cue (Witkin, Nichols, Terry & Katz, 1991) and selective D1 and D2 antagonists do not block it fully (Baker, Riddle, Saunders & Appel, 1993). These findings suggest that concurrent activity at both D1 and D2 receptor subtypes is necessary to produce the cocaine cue. Accordingly, it would be expected that simultaneous blockade of D1 and D2 receptors would be necessary to block cocaine's stimulus properties fully. The present study tested this hypothesis by examining the ability of various combinations of the D1 antagonist, Schering 23390, and the D2 antagonist, haloperidol, to block the cocaine cue in rats trained to discriminate cocaine (7.5 to 13 mg/kg) from distilled water in a water-reinforced operant procedure. Five of the six subjects tested displayed greater antagonism following a D1/D2 combination than following either antagonist alone which further supports the position that the concurrent activity of dopamine at both D1 and D2 receptors mediates the cocaine cue. The mechanism underlying this activity at the receptor subtypes, however, is unknown. That a D1/D2 agonist combination did not substitute for cocaine to any greater extent than each agonist alone (Spealman, Bergman, Madras & Melia, 1991) and that neither a D1 nor D2 antagonist blocked the cocaine cue consistently (present data) suggests that it is unlikely that this activity between D1 and D2 receptors is additive or synergistic in nature. Therefore, it is possible that other systems affected by cocaine (e.g., norepinepherine and serotonin) may be involved in mediating its stimulus properties. Given that norepinephrine and serotonin reuptake inhibitors have been shown to potentiate the discriminative properties of cocaine (Cunningham & Callahan, 1991), it is possible that these neurotransmitter systems may play some modulatory role in mediating cocaine's stimulus properties.Source: Dissertation Abstracts International, Volume: 55-11, Section: B, page: 5103.Ph.D. American University 1993.Englis
Immunolocalization of cyclin D1 in the developing lens of c-maf -/- mice
No full textThe maf gene encodes a transcription factor protein containing a typical basic/leucine zipper domain structure, a motif for protein dimerization and DNA binding. It has been demonstrated that maf family genes have important roles in embryonic development and cellular differentiation. In this study, localization of cyclin D1, one of the cell cycle-related molecules, was examined immunohistochemically in developing lens cells of c-maf knockout (-/-) mice. At embryonic day 14 in wild-type mice, lens cells consisted of round epithelial cells in a single layer and regularly arranged elongated lens cells, indicating primary lens fiber cells. Cyclin D1-positive nuclei were observed in the lens epithelial cells, whereas cyclin D1 was not detected in the primary lens fiber cells. In c-maf -/- mice, a variety of round epithelial cells were located in the anterior and posterior lens. Many cyclin D1-positive nuclei were observed in lens epithelial cells as well as posterior lens cells. These results are consistent with c-maf playing a role in the regulation of cyclin D1 in developing lens cells
Prognostic value of cyclin D1 expression in tumor-free surgical margins in head and neck squamous cell carcinomas
No full textConclusion: It was proved that cyclin D1-positive status in surgical margins was an independent prognostic indicator of local recurrence. The expression of cyclin D1 in tumor-free surgical margins may better predict local recurrence in patients with head and neck squamous cell carcinoma (HNSCC) after surgical treatment with curative intent. Objective: This retrospective study aimed to determine the prognostic indicators for local recurrence in HNSCC. Methods: A total of 116 HNSCC patients who underwent surgical treatment with curative intent and had histopathologically tumor-free margins were eligible for this study. The expression of p53 and cyclin D1 was assessed by immunohistochemical staining in surgical margins as well as in tumor specimens. Results: In all, 63 patients (54.3%) had p53-positive tumor specimens and 34 patients (29.3%) had p53-positive margins. Seventy-six patients (65.6%) had cyclin D1-positive tumor specimens and 54 patients (46.6%) had cyclin D1-positive margins. A significant difference in local control rates was observed between patients with cyclin D1-positive and -negative margins (77.2% vs 91.5%, log rank test, p = 0.0139). Multivariate Cox proportional hazards testing indicated that the hazard ratio of cyclin D1-positive margins for local recurrence was 4.58 (95% confidence interval 1.14–21.69, p = 0.0304)
Meet the Book Author: Quiet Revolutionaries
No full textIn our Meet the Book Author Series, the Journal of Law and Society and the Centre of Law and Society provide first-hand accounts from authors who have recently contributed notable socio-legal books to their respective fields. In this post, we hear from Sharon Thompson, whose new book Quiet Revolutionaries: The Married Women’s Association and Family Lawwas published in September 2022 with Bloomsbury
Milnacipran enhances the control of impulsive action by activating D1-like receptors in the infralimbic cortex
No full textRationale: Elevated impulsivity is often observed in patients with depression. We recently found that milnacipran, an antidepressant and a serotonin/noradrenaline reuptake inhibitor, could enhance impulse control in rats. However, the neural mechanisms underlying the effects of milnacipran on impulsive action remain unclear. Milnacipran increases not only extracellular serotonin and noradrenaline but also dopamine specifically in the medial prefrontal cortex, which is one of brain regions responsible for impulsive action. Objectives: Our goal was to identify whether D1-like and/or D2-like receptors in the infralimbic cortex (IL), the ventral portion of the medial prefrontal cortex, mediates the milnacipran-enhanced impulse control in a three-choice serial reaction time task. Methods: The rats were bilaterally injected with SCH23390, a selective D1-like receptor antagonist (0.3 or 3 ng/side) or eticlopride, a selective D2-like receptor antagonist (0.3 or 1 μg/side) into the IL after acute intraperitoneal administration of milnacipran (10 mg/kg). Results: Intra-IL SCH23390 injections reversed the milnacipran-enhanced impulse control, whereas injections of eticlopride into the IL failed to block the effects of milnacipran on impulsive action. Conclusions: This is the first report that demonstrates a critical role for D1-like receptors of the IL in milnacipran-enhanced control of impulsive action
Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D1-like receptors in neonatal rats
No full textBACKGROUND AND PURPOSE: Dopamine released from the endings of descending dopaminergic fibre in the spinal cord is suggested to be involved in modulating functions such as locomotion and nociception. Here, we examined the effects of dopamine on spinal synaptic transmissions in rats. EXPERIMENTAL APPROACH: Spinal reflex potentials, monosynaptic reflex potential (MSR) and slow ventral root potential (sVRP), were measured in the isolated spinal cord of the neonatal rat. Dopamine release was measured by using HPLC. KEY RESULTS: Dopamine at lower concentrations ( 1 μM), in addition to a potent sVRP depression, dopamine depolarized baseline potential and slightly depressed MSR. Depression of sVRP by dopamine was partially reversed by dopamine D1-like but not by D2-like receptor antagonists. SKF83959 and SKF81297, D1-like receptor agonists, and methamphetamine, an endogenous dopamine releaser, also caused the inhibition of sVRP. Methamphetamine also depressed MSR, which was inhibited by ketanserin, a 5-HT_[2A/2C] receptor antagonist. Methamphetamine induced the release of dopamine and 5-HT from spinal cords, indicating that the release of endogenous dopamine and 5-HT depresses sVRP and MSR respectively. CONCLUSION AND IMPLICATIONS: These results suggest that dopamine at lower concentrations preferentially inhibits sVRP, which is mediated via D1-like and unidentified receptors. The dopamine-evoked depression is involved in modulating the spinal functions by the descending dopaminergic pathways
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