miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression

Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type-1 (SCA1) neurodegenerative disease and some types of cancer; however, the role of CIC in prostate cancer remains unknown. Here we show that CIC suppresses prostate cancer progression. CIC expression was markedly decreased in human prostatic carcinoma. CIC overexpression suppressed prostate cancer cell proliferation, invasion, and migration, whereas CIC RNAi exerted opposite effects. We found that knock-down of CIC derepresses expression of ETV5 and CRABP1 in LNCaP and PC-3 cells, respectively, thereby promoting cell proliferation and invasion. We also discovered that miR-93, miR-106b, and miR-375, which are known to be frequently overexpressed in prostate cancer patients, cooperatively down-regulate CIC levels to promote cancer progression. Altogether, we suggest miR-93/miR-106b/miR-375-CIC-CRABP1 as a novel key regulatory axis in prostate cancer progression.113324Ysciescopu

Pim1 promotes human prostate cancer cell tumorigenicity and c-MYC transcriptional activity

<p>Abstract</p> <p>Background</p> <p>The serine/threonine kinase PIM1 has been implicated as an oncogene in various human cancers including lymphomas, gastric, colorectal and prostate carcinomas. In mouse models, Pim1 is known to cooperate with c-Myc to promote tumorigenicity. However, there has been limited analysis of the tumorigenic potential of Pim1 overexpression in benign and malignant human prostate cancer cells <it>in vivo</it>.</p> <p>Methods</p> <p>We overexpressed Pim1 in three human prostate cell lines representing different disease stages including benign (RWPE1), androgen-dependent cancer (LNCaP) and androgen-independent cancer (DU145). We then analyzed <it>in vitro </it>and <it>in vivo </it>tumorigenicity as well as the effect of Pim1 overexpression on c-MYC transcriptional activity by reporter assays and gene expression profiling using an inducible MYC-ER system. To validate that Pim1 induces tumorigenicity and target gene expression by modulating c-MYC transcriptional activity, we inhibited c-MYC using a small molecule inhibitor (10058-F4) or RNA interference.</p> <p>Results</p> <p>Overexpression of Pim1 alone was not sufficient to convert the benign RWPE1 cell to malignancy although it enhanced their proliferation rates when grown as xenografts <it>in vivo</it>. However, Pim1 expression enhanced the <it>in vitro </it>and <it>in vivo </it>tumorigenic potentials of the human prostate cancer cell lines LNCaP and DU145. Reporter assays revealed increased c-MYC transcriptional activity in Pim1-expressing cells and mRNA expression profiling demonstrated that a large fraction of c-MYC target genes were also regulated by Pim1 expression. The c-MYC inhibitor 10058-F4 suppressed the tumorigenicity of Pim1-expressing prostate cancer cells. Interestingly, 10058-F4 treatment also led to a reduction of Pim1 protein but not mRNA. Knocking-down c-MYC using short hairpin RNA reversed the effects of Pim1 on Pim1/MYC target genes.</p> <p>Conclusion</p> <p>Our results suggest an <it>in vivo </it>role of Pim1 in promoting prostate tumorigenesis although it displayed distinct oncogenic activities depending on the disease stage of the cell line. Pim1 promotes tumorigenicity at least in part by enhancing c-MYC transcriptional activity. We also made the novel discovery that treatment of cells with the c-MYC inhibitor 10058-F4 leads to a reduction in Pim1 protein levels.</p

Escherichia coli induces apoptosis and proliferation of mammary cells

Mammary cell apoptosis and proliferation were assessed after injection of Escherichia coli into the left mammary quarters of six cows. Bacteriological analysis of foremilk samples revealed coliform infection in the injected quarters of four cows. Milk somatic cell counts increased in these quarters and peaked at 24 h after bacterial injection. Body temperature also increased, peaking at 12 h postinjection, The number of apoptotic cells was significantly higher in the mastitic tissue than in the uninfected control. Expression of Bax and interleukin-1 beta converting enzyme increased in the mastitic tissue at 24 h and 72 h postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ significantly from the control at 72 h postinfection, Induction of matrix metalloproteinase-g, stromelysin-1 and urokinase-type plasminogen activator was also observed in the mastitic tissue. Moreover, cell proliferation increased in the infected tissue, These results demonstrate that Escherichia coli-induced mastitis promotes apoptosis and cell proliferation

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Factors associated with severe dry eye in primary Sjögren´s syndrome diagnosed patients

Introduction Primary Sjögren?s syndrome (pSS) is an autoimmune disease, characterized by lymphocytic infiltration of exocrine glands and other organs, resulting in dry eye, dry mouth and extraglandular systemic findings. Objective To explore the association of severe or very severe dry eye with extraocular involvement in patients diagnosed with primary Sjögren?s syndrome. Methods SJOGRENSER registry is a multicenter cross-sectional study of pSS patients. For the construction of our main variable, severe/very severe dry eye, we used those variables that represented a degree 3?4 of severity according to the 2007 Dry Eye Workshop classification. First, bivariate logistic regression models were used to identify the effect of each independent variable on severe/very severe dry eye. Secondly, multivariate analysis using regression model was used to establish the independent effect of patient characteristics. Results Four hundred and thirty-seven patients were included in SJOGRENSER registry; 94% of the patients complained of dry eye and 16% developed corneal ulcer. Schirmer?s test was pathological in 92% of the patients; 378 patients presented severe/very severe dry eye. Inflammatory articular involvement was significantly more frequent in patients with severe/very severe dry eye than in those without severe/very severe dry eye (82.5 vs 69.5%, p = 0,028). Inflammatory joint involvement was associated with severe/very severe dry eye in the multivariate analysis, OR 2.079 (95% CI 1.096?3.941). Conclusion Severe or very severe dry eye is associated with the presence of inflammatory joint involvement in patients with pSS. These results suggest that a directed anamnesis including systemic comorbidities, such as the presence of inflammatory joint involvement or dry mouth in patients with dry eye, would be useful to suspect a pSS

Segment-specific association between cervical pillar hyperplasia (CPH) and degenerative joint disease (DJD)

BACKGROUND: Cervical pillar hyperplasia (CPH) is a recently described phenomenon of unknown etiology and clinical significance. Global assessment of pillar hyperplasia of the cervical spine as a unit has not shown a relationship with degenerative joint disease, but a more sensible explanation of the architectural influence of CPH on cervical spine biomechanics may be segment-specific. OBJECTIVE: The objective of this study was to determine the level of association between degenerative joint disease (DJD) and cervical pillar hyperplasia (CPH) in an age- and gender-matched sample on a [cervical spine] by-level basis. RESEARCH METHODS: Two-hundred and forty radiographs were collected from subjects ranging in age between 40 and 69 years. The two primary outcome measures used in the study were the segmental presence/absence of cervical pillar hyperplasia from C3 to C6, and segment-specific presence/absence of degenerative joint disease from C1 to C7. Contingency Coefficients, at the 5% level of significance, at each level, were used to determine the strength of the association between CPH and DJD. Odds Ratios (OR) with their 95% Confidence Intervals (95% CI) were also calculated at each level to assess the strength of the association. RESULTS: Our study suggests that an approximately two-to-one odds, or a weak-to-moderate correlation, exists at C4 and C5 CPH and adjacent level degenerative disc disease (DDD); with the strongest (overall) associations demonstrated between C4 CPH and C4–5 DDD and between C5 CPH and C5–6 DDD. Age-stratified results demonstrated a similar pattern of association, even reaching the initially hypothesized OR ≥ 5.0 (95% CI > 1.0) or "moderately-strong correlation of C ≥ .4 (p ≤ .05)" in some age categories, including the 40–44, 50–59, and 60–64 years of age subgroups; these ORs were as follows: OR = 5.5 (95% CI 1.39–21.59); OR = 6.7 (95% CI 1.65–27.34); and OR = 5.3 (95% CI 1.35–21.14), respectively. CONCLUSION: Our results suggest that CPH has around two-to-one odds, that is, only a weak-to-moderate association with the presence of DJD (DDD component) at specific cervical spine levels; therefore, CPH may be but one of several factors that contributes (to a clinically important degree) to the development of DJD at specific levels in the cervical spine

Perpendicular Magnetic Anisotropy in FePt Patterned Media Employing a CrV Seed Layer

A thin FePt film was deposited onto a CrV seed layer at 400°C and showed a high coercivity (~3,400 Oe) and high magnetization (900–1,000 emu/cm3) characteristic of L10 phase. However, the magnetic properties of patterned media fabricated from the film stack were degraded due to the Ar-ion bombardment. We employed a deposition-last process, in which FePt film deposited at room temperature underwent lift-off and post-annealing processes, to avoid the exposure of FePt to Ar plasma. A patterned medium with 100-nm nano-columns showed an out-of-plane coercivity fivefold larger than its in-plane counterpart and a remanent magnetization comparable to saturation magnetization in the out-of-plane direction, indicating a high perpendicular anisotropy. These results demonstrate the high perpendicular anisotropy in FePt patterned media using a Cr-based compound seed layer for the first time and suggest that ultra-high-density magnetic recording media can be achieved using this optimized top-down approach

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

GPCR Genes Are Preferentially Retained after Whole Genome Duplication

One of the most interesting questions in biology is whether certain pathways have been favored during evolution, and if so, what properties could cause such a preference. Due to the lack of experimental evidence, whether select gene families have been preferentially retained over time after duplication in metazoan organisms remains unclear. Here, by syntenic mapping of nonchemosensory G protein-coupled receptor genes (nGPCRs which represent half the receptome for transmembrane signaling) in the vertebrate genomes, we found that, as opposed to the 8–15% retention rate for whole genome duplication (WGD)-derived gene duplicates in the entire genome of pufferfish, greater than 27.8% of WGD-derived nGPCRs which interact with a nonpeptide ligand were retained after WGD in pufferfish Tetraodon nigroviridis. In addition, we show that concurrent duplication of cognate ligand genes by WGD could impose selection of nGPCRs that interact with a polypeptide ligand. Against less than 2.25% probability for parallel retention of a pair of WGD-derived ligands and a pair of cognate receptor duplicates, we found a more than 8.9% retention of WGD-derived ligand-nGPCR pairs–threefold greater than one would surmise. These results demonstrate that gene retention is not uniform after WGD in vertebrates, and suggest a Darwinian selection of GPCR-mediated intercellular communication in metazoan organisms