MicroRNA-145 Targets YES and STAT1 in Colon Cancer Cells

BACKGROUND: MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-145 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of miR-145 in colon cancer, we have employed a microarray based approach to identify miR-145 targets. Based on seed site enrichment analyses and unbiased word analyses, we found a significant enrichment of miRNA binding sites in the 3'-untranslated regions (UTRs) of transcripts down-regulated upon miRNA overexpression. Gene Ontology analysis showed an overrepresentation of genes involved in cell death, cellular growth and proliferation, cell cycle, gene expression and cancer. A number of the identified miRNA targets have previously been implicated in cancer, including YES, FSCN1, ADAM17, BIRC2, VANGL1 as well as the transcription factor STAT1. Both YES and STAT1 were verified as direct miR-145 targets. CONCLUSIONS/SIGNIFICANCE: The study identifies and validates new cancer-relevant direct targets of miR-145 in colon cancer cells and hereby adds important mechanistic understanding of the tumor-suppressive functions of miR-145

Social Interactions vs Revisions, What is important for Promotion in Wikipedia?

In epistemic community, people are said to be selected on their knowledge contribution to the project (articles, codes, etc.) However, the socialization process is an important factor for inclusion, sustainability as a contributor, and promotion. Finally, what does matter to be promoted? being a good contributor? being a good animator? knowing the boss? We explore this question looking at the process of election for administrator in the English Wikipedia community. We modeled the candidates according to their revisions and/or social attributes. These attributes are used to construct a predictive model of promotion success, based on the candidates's past behavior, computed thanks to a random forest algorithm. Our model combining knowledge contribution variables and social networking variables successfully explain 78% of the results which is better than the former models. It also helps to refine the criterion for election. If the number of knowledge contributions is the most important element, social interactions come close second to explain the election. But being connected with the future peers (the admins) can make the difference between success and failure, making this epistemic community a very social community too

A novel knee prosthesis model of implant-related osteo- myelitis in rats

Background and purpose: There have been numerous reports of animal models of osteomyelitis. Very few of these have been prosthesis models that imitate human conditions. We have developed a new rat model of implant-related osteomyelitis that mimics human osteomyelitis, to investigate the pathology of infection after orthop edic implant surgery. Methods: 2 wild-type strains of Staphylococcus aureus, MN8 and UAMS-1, and their corresponding mutants that are unable to produce poly-N-acetyl glucosamine (PNAG) (ica::tet) were injected into the medullary canals of the femur and tibia at 3 different doses: $10^2$, $10^3$, and > $10^4$ CFU/rat. We measured clinical signs, inflammatory markers, radiographic signs, histopathology, and bacteriology in the infected animals. Results: An inoculum of at least $10^4$ cfu of either wild-type bacterial strain resulted in histological, bacteriological, and radiographic signs of osteomyelitis with loosening of the prosthesis. An inoculum of $10^3$ CFU gave signs of osteomyelitis but the prosthesis remained in situ. Bacterial inocula of $10^2$ cfu gave no signs of osteolysis. Interpretation: We have established a new knee prosthesis model that is suitable for reliable induction of experimental implant-associated osteomyelitis with the prosthesis in situ, using a small inoculum of S. aureus. At a dose of $10^3$ CFU/rat, bacteria unable to produce PNAG (ica::tet) had only minor defects in their virulence

Acquisition of Ca2+ and HCO3−/CO32− for shell formation in embryos of the common pond snail Lymnaea stagnalis

Embryos of the freshwater common pond snail Lymnaea stagnalis develop to hatch within 10 days under control conditions (22°C, Miami-Dade tap water) and this development is impaired by removal of ambient calcium. In contrast, embryos did not exhibit dependence upon an ambient HCO3−/CO32− source, developing and hatching in HCO3−/CO32−-free water at rates comparable to controls. Post-metamorphic, shell-laying embryos exhibited a significant saturation-type calcium uptake as a function of increasing ambient calcium concentration. However, changes in ambient bicarbonate concentration did not influence calcium or apparent titratable alkalinity uptake. There was a distinct shift from no significant flux in pre-metamorphic embryos to net uptake of calcium in post-metamorphic stages as indicated by an increased uptake from the micro-environment surrounding the egg mass and increased net uptake in 24-h, whole egg mass flux measurements. Furthermore, HCO3−/CO32− acquisition as measured by titratable alkalinity flux is at least partially attributable to an endogenous carbonate source that is associated with acid extrusion. Thus, calcium requirements for embryonic shell formation are met via uptake but HCO3−/CO32−, which is also necessary for shell formation is acquired in part from endogenous sources with no detectable correlation to ambient HCO3−/CO32− availability

The Secret to Successful User Communities: An Analysis of Computer Associates’ User Groups

This paper provides the first large scale study that examines the impact of both individual- and group-specific factors on the benefits users obtain from their user communities. By empirically analysing 924 survey responses from individuals in 161 Computer Associates' user groups, this paper aims to identify the determinants of successful user communities. To measure success, the amount of time individual members save through having access to their user networks is used. As firms can significantly profit from successful user communities, this study proposes four key implications of the empirical results for the management of user communities

Wasp Hawking Induces Endothermic Heat Production in Guard Bees

When vespine wasps, Vespa velutina Lepeletier (Hymenoptera: Vespidae), hawk (capture) bees at their nest entrances alerted and poised guards of Apis cerana cerana F. and Apis mellifera ligustica Spinola (Hymenoptera: Apidae) have average thoracic temperatures slightly above 24° C. Many additional worker bees of A. cerana, but not A. mellifera, are recruited to augment the guard bee cohort and begin wing-shimmering and body-rocking, and the average thoracic temperature rises to 29.8 ± 1.6° C. If the wasps persist hawking, about 30 guard bees of A. cerana that have raised their thoracic temperatures to 31.4 ± 0.9° C strike out at a wasp and form a ball around it. Within about three minutes the core temperature of the heat-balling A. cerana guard bees reaches about 46° C, which is above the lethal limit of the wasps, which are therefore killed. Although guard bees of A. mellifera do not exhibit the serial behavioural and physiological changes of A. cerana, they may also heat-ball hawking wasps. Here, the differences in the sequence of changes in the behaviour and temperature during “resting” and “heat-balling” by A. cerana and A. mellifera are reported

Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.

Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders

Consensus review of best practice of transanal irrigation in adults

Study design: Review article. Objectives: To provide a consensus expert review of the treatment modality for transanal irrigation (TAI). Methods: A consensus group of specialists from a range of nations and disciplines who have experience in prescribing and monitoring patients using TAI worked together assimilating both the emerging literature and rapidly accruing clinical expertise. Consensus was reached by a round table discussion process, with individual members leading the article write-up in the sections where they had particular expertise. Results: Detailed trouble-shooting tips and an algorithm of care to assist professionals with patient selection, management and follow-up was developed. Conclusion: This expert review provides a practical adjunct to training for the emerging therapeutic area of TAI. Careful patient selection, directly supervised training and sustained follow-up are key to optimise outcomes with the technique. Adopting a tailored, stepped approach to care is important in the heterogeneous patient groups to whom TAI may be applied. Sponsorship: The review was financially supported by Coloplast A/S. Spinal Cord (2013) 51, 732–738; doi:10.1038/sc.2013.86; published online 20 August 201

Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

Study question: Is methylphenidate beneficial or harmful for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents? / Methods: Electronic databases were searched up to February 2015 for parallel and crossover randomised clinical trials comparing methylphenidate with placebo or no intervention in children and adolescents with ADHD. Meta-analyses and trial sequential analyses (TSA) were conducted. Quality was assessed using GRADE. Teachers, parents, and observers rated ADHD symptoms and general behaviour. / Study answer and limitations: The analyses included 38 parallel group trials (n=5111, median treatment duration 49 days) and 147 crossover trials (n=7134, 14 days). The average age across all studies was 9.7 years. The analysis suggested a beneficial effect of methylphenidate on teacher rated symptoms in 19 parallel group trials (standardised mean difference (SMD) −0.77, n=1698), corresponding to a mean difference of −9.6 points on the ADHD rating scale. There was no evidence that methylphenidate was associated with an increase in serious adverse events (risk ratio 0.98, nine trials, n=1532; TSA adjusted intervention effect RR 0.91). Methylphenidate was associated with an increased risk of non-serious adverse events (1.29, 21 trials, n=3132; TSA adjusted RR 1.29). Teacher rated general behaviour seemed to improve with methylphenidate (SMD −0.87, five trials, n=668) A change of 7 points on the child health questionnaire (CHQ) has been deemed a minimal clinically relevant difference. The change reported in a meta-analysis of three trials corresponds to a mean difference of 8.0 points on the CHQ (range 0-100 points), which suggests that methylphenidate may improve parent reported quality of life (SMD 0.61, three trials, n=514). 96.8% of trials were considered high risk of bias trials according to the Cochrane guidelines. All outcomes were assessed very low quality according to GRADE. / What this study adds: The results suggest that among children and adolescents with a diagnosis of ADHD, methylphenidate may improve teacher reported symptoms of ADHD and general behaviour and parent reported quality of life. However, given the risk of bias in the included studies, and the very low quality of outcomes, the magnitude of the effects is uncertain. Methylphenidate is associated with an increased risk of non-serious but not serious adverse events. / Funding, competing interests, data sharing: Region Zealand Research Foundation and Copenhagen Trial Unit. Competing interests are given in the full paper on bmj.com. Full data are available in the version of this review published in The Cochrane Library