RNA-binding proteins play a key role in post-transcriptional regulation of mRNA stability and translation. We have identified that RBM3, a translation regulatory protein, is significantly upregulated ...in human tumors, including a stage-dependent increase in colorectal tumors. Forced RBM3 overexpression in NIH3T3 mouse fibroblasts and SW480 human colon epithelial cells increases cell proliferation and development of compact multicellular spheroids in soft agar suggesting the ability to induce anchorage-independent growth. In contrast, downregulating RBM3 in HCT116 colon cancer cells with specific siRNA decreases cell growth in culture, which was partially overcome when treated with prostaglandin E(2), a product of cyclooxygenase (COX)-2 enzyme activity. Knockdown also resulted in the growth arrest of tumor xenografts. We have also identified that RBM3 knockdown increases caspase-mediated apoptosis coupled with nuclear cyclin B1, and phosphorylated Cdc25c, Chk1 and Chk2 kinases, implying that under conditions of RBM3 downregulation, cells undergo mitotic catastrophe. RBM3 enhances COX-2, IL-8 and VEGF mRNA stability and translation. Conversely, RBM3 knockdown results in loss in the translation of these transcripts. These data demonstrate that the RNA stabilizing and translation regulatory protein RBM3 is a novel proto-oncogene that induces transformation when overexpressed and is essential for cells to progress through mitosis.
•A novel approach to generate functionally graded cellular structures was evaluated.•The relationships between the method parameters and cell size were investigated.•Variation in cell edge length was ...greatest for the Voronoi connection scheme.•There was approximately an 8% underestimation of cell area for both target regions.•Practical implementation implications were discussed for tackling 3D problems.
The spatial variation of cell size in a functionally graded cellular structure is achieved using error diffusion to convert a continuous tone image into binary form. Effects of two control parameters, greyscale value and resolution on the resulting cell size measures were investigated. Variation in cell edge length was greatest for the Voronoi connection scheme, particularly at certain parameter combinations. Relationships between these parameters and cell size were identified and applied to an example, where the target was to control the minimum and maximum cell size. In both cases there was an 8% underestimation of cell area for target regions.
Clinically, osteopenia or low bone mass has been observed in a variety of chronic inflammatory diseases, and elevated proinflammatory mediators have implicated this process. The purpose of this study ...was to develop an in vivo model of bone loss induced by chronic systemic inflammation. Time-release pellets designed to deliver one of three doses of LPS: Low (3.3 μg/day), High (33.3 μg/day), or Placebo over 90 days, were implanted subcutaneously in 3-month-old male Sprague–Dawley rats (
n = 8/group). Neutrophil counts, indicative of ongoing inflammation, were elevated (
P < 0.05) in both LPS groups at 30 days post-implant and remained significantly elevated in the High dose throughout the 90-day study period. At the end of the study, bone loss occurred in the femur as indicated by decreased bone mineral density (BMD) in both LPS-treated groups, but vertebral BMD was reduced in the High dose animals only. Microcomputed tomography revealed that trabecular bone volume (BV/TV) of the proximal tibial metaphysis tended to be reduced in the High dose LPS group. Deleterious effects on trabecular number (TbN) and trabecular separation (TbSp) were observed in both LPS-treated groups, but only the High dose group reached statistical significance. These alterations in trabecular microarchitecture resulted in compromised biomechanical properties. No changes in cortical thickness, porosity, or area of the tibia midshaft were evident at either dose of LPS. Up-regulation of the proinflammatory mediators, cyclooxygenase (COX)-2, interleukin (IL)-1, and tumor necrosis factor (TNF)-α was demonstrated in the metaphyseal region where the deleterious effects of LPS were observed. In addition to these alterations in bone, trichrome staining indicated changes in the coronary arterioles, consistent with vascular disease. Utilization of a LPS time-release pellet appears to provide an in vivo model of chronic inflammation-induced bone loss and a potentially novel system to study concurrent development of osteopenia and vascular disease.
Previously, dietary supplementation with dried plums, a rich source of polyphenolic compounds with antioxidant and anti-inflammatory properties, has been shown to improve bone density, microstructure ...and biomechanics in female animal models of osteopenia. We designed this study to determine the extent to which dried plum prevents skeletal deterioration in gonadal hormone deficient male animals and to begin to understand its mechanism of action. Sixty 6-month-old male Sprague–Dawley rats were either sham-operated (Sham=1 group) or orchidectomized (ORX=4 groups) and randomly assigned to dietary treatments: standard semi-purified diet (Control) with either LD=5%, MD=15%, or HD=25% (w/w) dried plum for 90 days. At the end of the treatment period, both the MD and HD dried plum completely prevented the ORX-induced decrease in whole body, femur, and lumbar vertebra bone mineral density (BMD). Biomechanical testing indicated that the MD and HD of dried plum prevented the ORX-induced decrease in ultimate load of the cortical bone as well as the compressive force and stiffness of trabecular bone within the vertebrae. Analyses of trabecular microarchitecture of the distal femur metaphysis and vertebral body revealed that HD dried plum protected against the decrease in trabecular bone volume (BV/TV) induced by ORX. In the distal femur, all doses of dried plum improved trabecular number (TbN) and separation (TbSp) compared to the ORX-control group, while MD and HD dried plum prevented the ORX-induced changes in vertebral TbN and TbSp. At the end of the 90-day treatment, no remarkable changes in serum osteocalcin or alkaline phosphatase in any of the treatment groups were observed, while serum insulin-like growth factor (IGF)-I was increased by dried plum. The ORX-induced increase in urinary deoxypyridinoline (DPD) excretion was completely prevented by all doses of dried plum coinciding with down-regulation of gene expression for receptor activator of NFκ-B ligand (RANKL) and osteoprotegerin (OPG) in the bone. We conclude that dried plum prevents osteopenia in androgen deficient male rats, and these beneficial effects may be attributed in part to a decrease in osteoclastogenesis via down-regulation of RANKL and stimulation of bone formation mediated by IGF-I.
This study investigated the convergent, discriminant, and incremental validity of one ability test of emotional intelligence (EI)—the Mayer-Salovey-Caruso-Emotional Intelligence Test (MSCEIT)—and two ...self-report measures of EI—the Emotional Quotient Inventory (EQ-i) and the self-report EI test (SREIT). The MSCEIT showed minimal relations to the EQ-i and SREIT, whereas the latter two measures were moderately interrelated. Among EI measures, the MSCEIT was discriminable from well-studied personality and well-being measures, whereas the EQ-i and SREIT shared considerable variance with these measures. After personality and verbal intelligence were held constant, the MSCEIT was predictive of social deviance, the EQ-i was predictive of alcohol use, and the SREIT was inversely related to academic achievement. In general, results showed that ability EI and self-report EI are weakly related and yield different measurements of the same person.
Bone loss was confirmed after 90 days in 50 6-month-old male Sprague Dawley rats that were sham-operated or orchidectomized (ORX). In this study, we have shown that dried plum (DP) has potent effects ...on bone in terms of bone mass, microarchitecture, and strength in osteopenic male rats. Although these changes may be mediated through the suppression of bone resorption, the fact that the restoration in some of the bone structural and biomechanical parameter shares some similarities with parathyroid hormone (PTH) should not be overlooked. Further investigation is needed on a mechanistic level to clarify the influence of DP on bone metabolism.
This study was designed to investigate the extent to which DP reverses bone loss in osteopenic ORX rats and to compare its effects to PTH.
Fifty, 6-month-old male Sprague Dawley rats were sham-operated or ORX, and bone loss was confirmed after 90 days. The ORX groups were assigned to control (AIN-93M) diet, 25% DP diet, or PTH (80 microg/kg) for 90 days.
DP induced an 11% increase in vertebral and femoral BMD compared to ORX-controls. BMD in the PTH-treated group was increased by 20.7% (vertebra) and 17.9% (femur). Vertebral trabecular bone volume (BV/TV) and number were increased by DP and trabecular separation was decreased compared to controls, which were similar to PTH. Alterations in trabecular bone of the femur were similar to those in the vertebra, but DP did not restore BV/TV to the same extent. Cortical thickness was improved by DP and further enhanced by PTH. DP tended to decrease urinary deoxypyridinoline and calcium, but did not alter alkaline phosphatase or osteocalcin.
We conclude that though the degree of improvement was not equivalent to PTH with regard to all parameters, DP reverses bone loss due to ORX and the mechanisms should be further investigated.
This study assessed the discriminant, criterion and incremental validity of an ability measure of emotional intelligence (EI). College students (
N=330) took an ability test of EI, a measure of the ...Big Five personality traits, and provided information on Life Space scales that assessed an array of self-care behaviours, leisure pursuits, academic activities, and interpersonal relations. Women scored significantly higher in EI than men. EI, however, was more predictive of the Life Space criteria for men than for women. Lower EI in males, principally the inability to perceive emotions and to use emotion to facilitate thought, was associated with negative outcomes, including illegal drug and alcohol use, deviant behaviour, and poor relations with friends. The findings remained significant even after statistically controlling for scores on the Big Five and academic achievement. In this sample, EI was significantly associated with maladjustment and negative behaviours for college-aged males, but not for females.
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•Blast TBI-induced vestibulomotor deficits occur within a certain range for animal models.•Behavioral deficits post blast TBI correlate with increases in N/OFQ and NOP in plasma and ...brain.•A single treatment with SB-612111 delayed behavior deficits and prevented cerebral hypoxia.
Mild traumatic brain injury (mTBI) diagnoses have increased due to aggressive sports and blast-related injuries, but the cellular mechanisms and pathology underlying mTBI are not completely understood. Previous reports indicate that Nociceptin Orphanin/FQ (N/OFQ), an endogenous neuropeptide, contributes to post-injury ischemia following mechanical brain injury, yet its specific role in cerebral hypoxia, vestibulomotor function and injury marker expression following blast-induced TBI is not known. This study is the first to identify a direct association of N/OFQ and its N/OFQ peptide (NOP) receptor with TBI-induced changes following a single 80psi head blast exposure in male rats. N/OFQ and NOP receptor expression increased in brain tissue and plasma following TBI, concurrent with vestibular dysfunction but preceding hypoxia and appearance of injury markers compared to sham rats. A single post-blast treatment with the NOP receptor antagonist, SB-612111, transiently improved acute vestibulomotor performance. It also prevented increases in markers of TBI-induced hypoxia, pro-apoptotic proteins and injury seen 8–10days post-blast. This study reveals an apparent role for the N/OFQ-NOP receptor system in blast TBI and suggests potential therapeutic utility of NOP receptor antagonists for mTBI.
Prohibitin is a candidate tumor suppressor gene located on human chromosome 17q21, a region of frequent loss of heterozygosity in breast cancers. We showed previously that microinjection of RNA ...encoded by the prohibitin gene 3'untranslated region (3'UTR) blocks the G(1)-S transition causing cell cycle arrest in several human cancer cell lines, including MCF7. Two allelic forms (C versus T) of the prohibitin 3'UTR exist, and carriers of the less common variant (Tallele) with a family history of breast cancer exhibited an increased risk of breast cancer. In the present study, we examined the tumor suppressor activity of the prohibitin 3'UTR in human breast cancer cells. Stable clones of MCF7 cells expressing either the C allele or the T allele RNA under the control of the cytomegalovirus promoter were isolated and compared with empty vector clones. Clones expressing the C allele RNA (UTR/C) exhibited significant suppression of growth in cell proliferation assays, inhibition of colony formation in soft agar assays, and suppression of xenograft tumor growth when implanted on nude mice, compared with either T allele expressing or empty vector clones. Immunohistochemical analyses with Ki67 staining confirmed a significant reduction in proliferation of UTR/C tumors. Thus, the C allele of prohibitin 3'UTR produces a functional RNA, whereas a single nucleotide polymorphism creates a null allele (T allele) of which the RNA product has lost activity. Our data demonstrate for the first time that an RNA molecule functions as a tumor suppressor in human breast cancer.
Raw ground beef patties inoculated with stationary-phase cells of Escherichia coli O157:H7, salmonellae, or Campylobacter jejuni were subjected to gamma irradiation (60Co) treatment, with doses ...ranging from 0 to 2.52 kGy. The influence of two levels of fat (8 to 14% low fat and 27 to 28% high fat) and temperature (frozen -17 to -15 degrees C and refrigerated 3 to 5 degrees C) on the inactivation of each pathogen by irradiation was investigated. In ascending order of irradiation resistance, the D10 values ranged from 0.175 to 0.235 kGy (C. jejuni), from 0.241 to 0.307 kGy (E. coli O157:H7), and from 0.618 to 0.800 kGy (salmonellae). Statistical analysis revealed that E. coli O157:H7 had a significantly (P 0.05) higher D10 value when irradiated at -17 to -15 degrees C than when irradiated at 3 to 5 degrees C. Regardless of the temperature during irradiation, the level of fat did not have a significant effect on the D10 value. Salmonellae behaved like E. coli O157:H7 in low-fat beef, but temperature did not have a significant effect when the pathogen was irradiated in high-fat ground beef. Significantly higher D10 values were calculated for C. jejuni irradiated in frozen than in refrigerated low-fat beef. C. jejuni was more resistant to irradiation in low-fat beef than in high-fat beef when treatment was at -17 to -15 degrees C. Regardless of the fat level and temperature during inactivation, these pathogens were highly sensitive to gamma irradiation. An applied dose of 2.5 kGy would be sufficient to kill 10(8.1) E. coli O157:H7, 10(3.1) salmonellae, and 10(10.6) C. jejuni, resulting in a high probability of complete inactivation of populations much higher than those occasionally present in ground beef patties
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