The Ubiquitin Peptidase UCHL1 Induces G0/G1 Cell Cycle Arrest and Apoptosis Through Stabilizing p53 and Is Frequently Silenced in Breast Cancer

Background: Breast cancer (BrCa) is a complex disease driven by aberrant gene alterations and environmental factors. Recent studies reveal that abnormal epigenetic gene regulation also plays an important role in its pathogenesis. Ubiquitin carboxyl- terminal esterase L1 (UCHL1) is a tumor suppressor silenced by promoter methylation in multiple cancers, but its role and alterations in breast tumorigenesis remain unclear. Methodology/Principal Findings: We found that UCHL1 was frequently downregulated or silenced in breast cancer cell lines and tumor tissues, but readily expressed in normal breast tissues and mammary epithelial cells. Promoter methylation of UCHL1 was detected in 9 of 10 breast cancer cell lines (90%) and 53 of 66 (80%) primary tumors, but rarely in normal breast tissues, which was statistically correlated with advanced clinical stage and progesterone receptor status. Pharmacologic demethylation reactivated UCHL1 expression along with concomitant promoter demethylation. Ectopic expression of UCHL1 significantly suppressed the colony formation and proliferation of breast tumor cells, through inducing G0/G1 cell cycle arrest and apoptosis. Subcellular localization study showed that UCHL1 increased cytoplasmic abundance of p53. We further found that UCHL1 induced p53 accumulation and reduced MDM2 protein level, and subsequently upregulated the expression of p21, as well as cleavage of caspase3 and PARP, but not in catalytic mutant UCHL1 C90Sexpressed cells

Healthcare providers' knowledge, experience and challenges of reporting adverse events following immunisation: a qualitative study

Background: Healthcare provider spontaneous reporting of suspected adverse events following immunisation (AEFI) is central to monitoring post-licensure vaccine safety, but little is known about how healthcare professionals recognise and report to surveillance systems. The aim of this study was explore the knowledge, experience and attitudes of medical and nursing professionals towards detecting and reporting AEFI. Methods: We conducted a qualitative study, using semi-structured, face to face interviews with 13 Paediatric Emergency Department consultants from a tertiary paediatric hospital, 10 General Practitioners, 2 local council immunisation and 4 General Practice nurses, recruited using purposive sampling in Adelaide, South Australia, between December 2010 and September 2011. We identified emergent themes related to previous experience of an AEFI in practice, awareness and experience of AEFI reporting, factors that would facilitate or impede reporting and previous training in vaccine safety. Thematic analysis was used to analyse the data. Results: AEFI reporting was infrequent across all groups, despite most participants having reviewed an AEFI. We found confusion about how to report an AEFI and variability, according to the provider group, as to the type of events that would constitute a reportable AEFI. Participants’ interpretation of a “serious” or “unexpected” AEFI varied across the three groups. Common barriers to reporting included time constraints and unsatisfactory reporting processes. Nurses were more likely to have received formal training in vaccine safety and reporting than medical practitioners. Conclusions: This study provides an overview of experience and beliefs of three healthcare professional groups in relation to identifying and reporting AEFI. The qualitative assessment reveals differences in experience and awareness of AEFI reporting across the three professional groups. Most participants appreciated the importance of their role in AEFI surveillance and monitoring the ongoing safety of vaccines. Future initiatives to improve education, such as increased training to health care providers, particularly, medical professionals, are required and should be included in both undergraduate curricula and ongoing, professional development.Adriana Parrella, Annette Braunack-Mayer, Michael Gold, Helen Marshall and Peter Baghurs

Crickets are not a free lunch: protein capture from scalable organic side-streams via high-density populations of Acheta domesticus.

It has been suggested that the ecological impact of crickets as a source of dietary protein is less than conventional forms of livestock due to their comparatively efficient feed conversion and ability to consume organic side-streams. This study measured the biomass output and feed conversion ratios of house crickets (Acheta domesticus) reared on diets that varied in quality, ranging from grain-based to highly cellulosic diets. The measurements were made at a much greater population scale and density than any previously reported in the scientific literature. The biomass accumulation was strongly influenced by the quality of the diet (p<0.001), with the nitrogen (N) content, the ratio of N to acid detergent fiber (ADF) content, and the crude fat (CF) content (y=N/ADF+CF) explaining most of the variability between feed treatments (p = 0.02; R2 = 0.96). In addition, for populations of crickets that were able to survive to a harvestable size, the feed conversion ratios measured were higher (less efficient) than those reported from studies conducted at smaller scales and lower population densities. Compared to the industrial-scale production of chickens, crickets fed a poultry feed diet showed little improvement in protein conversion efficiency, a key metric in determining the ecological footprint of grain-based livestock protein. Crickets fed the solid filtrate from food waste processed at an industrial scale via enzymatic digestion were able to reach a harvestable size and achieve feed and protein efficiencies similar to that of chickens. However, crickets fed minimally-processed, municipal-scale food waste and diets composed largely of straw experienced >99% mortality without reaching a harvestable size. Therefore, the potential for A. domesticus to sustainably supplement the global protein supply, beyond what is currently produced via grain-fed chickens, will depend on capturing regionally scalable organic side-streams of relatively high-quality that are not currently being used for livestock production

ANOVA for the regression depicted in Fig. 2.

<p>The mg i^-1 of <i>A</i>. <i>domesticus</i> at 30 days after hatching is explained (p = 0.02; R² = 0.96) by the ratio of nitrogen (N) to acid detergent fiber content (ADF) plus the proportional crude fat content (CF), [(N/ADF) + CF], in the feed substrate treatments. See [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118785#pone.0118785.ref036" target="_blank">36</a>] for explanation of terms.</p><p>ANOVA for the regression depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118785#pone.0118785.g002" target="_blank">Fig. 2</a>.</p

ANOVA for the regression depicted in Fig. 2.

<p>The mg i^-1 of <i>A</i>. <i>domesticus</i> at 30 days after hatching is explained (p = 0.02; R² = 0.96) by the ratio of nitrogen (N) to acid detergent fiber content (ADF) plus the proportional crude fat content (CF), [(N/ADF) + CF], in the feed substrate treatments. See [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118785#pone.0118785.ref036" target="_blank">36</a>] for explanation of terms.</p><p>ANOVA for the regression depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118785#pone.0118785.g002" target="_blank">Fig. 2</a>.</p

Biomass response of <i>A</i>. <i>domesticus</i> to variation in diet.

<p>Biomass accumulation (mg i^-1) over time for populations of <i>A</i>. <i>domesticus</i> receiving Poultry Feed (PF), Food Waste 1 (FW1), Food Waste 2 (FW2), Crop Residue 1 (CR1), or Crop Residue 2 (CR2) diets (left hand axis), and harvested, fresh weight biomass (g / 1.2 m²) for PF and FW1 treatments (right hand axis). Vertical lines represent the standard error of the mean between the three replications per treatment.</p

The effect of feed quality on the biomass response of <i>A</i>. <i>domesticus</i>.

<p>Depicts the relationship between feed quality and the biomass response of <i>A</i>. <i>domesticus</i> populations at 30 days after hatching, where feed quality is characterized by the proportion of nitrogen (N) to acid detergent fiber content (ADF) plus the proportional crude fat content (CF) [y = (N/ADF) + CF] in the feed substrate treatments (p = 0.02; R² = 0.96). Vertical lines represent the standard error of the mean between the three replications per treatment. For ANOVA see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118785#pone.0118785.t002" target="_blank">Table 2</a>. See [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118785#pone.0118785.ref036" target="_blank">36</a>] for explanation of terms.</p

Experimental arena for confining thrips and other small arthropods in the laboratory

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