IR-Based Publishing Initiatives: Stories of Success and Lessons Learned

In this panel discussion, we will learn from several editors who are using the University of Southern Mississippi\u27s institutional repository, Aquila, as a publishing platform for an array of journals, ranging from a peer-reviewed journal with a publication history of over fifty years to newly-launched disciplinary journals to a multidisciplinary journal of undergraduate research. We will discuss the backgrounds of each publication, as well as some of the workflows these editors are using to manage the publications that they represent

An appropriate tool for entrepreneurial learning in SMEs? The case of the 20Twenty Leadership Programme

The 20Twenty Leadership Programme was developed by Cardiff Metropolitan University as an executive education programme to be delivered within South Wales to small businesses. It is funded by the European Social Fund (ESF) and administered by the Welsh European Funding Office and has the key aim of developing SME’s growth potential via a range of leadership and management skills, including a focus on ‘soft’ skills. The focus of this paper is to place the 20Twenty Leadership Programme within the wider context of entrepreneurship policy and SME training initiatives in particular, and then to examine the rationale and delivery methods of the Programme in relation to these. It also reflects on the Programme’s success (or otherwise) to date where possible. Finally, the paper seeks to suggest fruitful areas of further research both in terms of the 20Twenty Leadership Programme itself, but also with regard to evaluation in relation to other parallel programmes, and to SME training initiatives more generally

The distribution of calmodulin in living mitotic cells

Calmodulin has been labeled with rhodamine isothiocyanate (CaM-RITC) and used as a probe for the location of calmodulin in vivo. CaM-RITC retains its capacity to regulate the activity of brain phosphodiesterase in a Ca2+-dependent manner in vitro, indicating that the labeled protein is still active. After injection into living mammalian cells CaM-RITC incorporates rapidly into the mitotic spindle; the details of its localization there mimic closely the distribution of Calmodulin seen by immunofluorescence. In interphase cells the CaM-RITC is excluded from the nucleus, but shows no region of specific concentration within the cytoplasm. Neither a 2-fold increase in cellular CaM nor the injection of anti CaM has any observable effect on the progress of mitosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25048/1/0000476.pd

Incorporating tumour pathology information into breast cancer risk prediction algorithms.

INTRODUCTION: Mutations in BRCA1 and BRCA2 confer high risks of breast cancer and ovarian cancer. The risk prediction algorithm BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) may be used to compute the probabilities of carrying mutations in BRCA1 and BRCA2 and help to target mutation screening. Tumours from BRCA1 and BRCA2 mutation carriers display distinctive pathological features that could be used to better discriminate between BRCA1 mutation carriers, BRCA2 mutation carriers and noncarriers. In particular, oestrogen receptor (ER)-negative status, triple-negative (TN) status, and expression of basal markers are predictive of BRCA1 mutation carrier status. METHODS: We extended BOADICEA by treating breast cancer subtypes as distinct disease end points. Age-specific expression of phenotypic markers in a series of tumours from 182 BRCA1 mutation carriers, 62 BRCA2 mutation carriers and 109 controls from the Breast Cancer Linkage Consortium, and over 300,000 tumours from the general population obtained from the Surveillance Epidemiology, and End Results database, were used to calculate age-specific and genotype-specific incidences of each disease end point. The probability that an individual carries a BRCA1 or BRCA2 mutation given their family history and tumour marker status of family members was computed in sample pedigrees. RESULTS: The cumulative risk of ER-negative breast cancer by age 70 for BRCA1 mutation carriers was estimated to be 55% and the risk of ER-positive disease was 18%. The corresponding risks for BRCA2 mutation carriers were 21% and 44% for ER-negative and ER-positive disease, respectively. The predicted BRCA1 carrier probabilities among ER-positive breast cancer cases were less than 1% at all ages. For women diagnosed with breast cancer below age 50 years, these probabilities rose to more than 5% in ER-negative breast cancer, 7% in TN disease and 24% in TN breast cancer expressing both CK5/6 and CK14 cytokeratins. Large differences in mutation probabilities were observed by combining ER status and other informative markers with family history. CONCLUSIONS: This approach combines both full pedigree and tumour subtype data to predict BRCA1/2 carrier probabilities. Prediction of BRCA1/2 carrier status, and hence selection of women for mutation screening, may be substantially improved by combining tumour pathology with family history of cancer.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Effects of alcohol and nicotine on cytotoxic functions of human lymphocytes

The in vitro effects of the recreational drugs, ethanol (EtOH) and nicotine, on natural killer (NK) antibody-dependent cellular cytotoxic (ADCC) and lymphokine-activated killer (LAK) cell activities on normal lymphocytes were investigated. Lymphocytes precultured with EtOH at concentrations of 0.4 and 0.6% (v/v) produced significant suppression of NK and ADCC activities. In target-binding assays, EtOH decreased the target-binding capacity of effector cells. EtOH also inhibited the activities of Percoll-separated, NK-enriched large granular lymphocytes. EtOH-induced inhibition of NK activity could be reversed by incubating lymphocytes for 1 hr with interferon. The generation and lytic capacity of LAK cells was also significantly depressed by EtOH when added at the initiation of culture. Nicotine at concentrations of 5 and 10 [mu]g/ml, when added directly to mixtures of effector and target cells, produced significant inhibition of NK activity. Nicotine (2 [mu]g/ml) and EtOH (0.01, 0.1, and 0.2%) at noninhibitory concentrations when added separately, showed significant suppression of NK activity when used in combination. Pretreatment of target cells with either EtOH or nicotine for 4 hr did not affect cytotoxic activity. Inhibition of cytotoxicity was also not due to direct toxicity of effector cells because lymphocytes treated with either EtOH or nicotine showed normal 51Cr release and their viability was comparable to that of untreated control cells. These studies demonstrate that EtOH and nicotine have significant immunomodulatory effects on the cytotoxic activities of human lymphocytes which may be of clinical relevance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28716/1/0000537.pd

REVEILLE8 and PSEUDO-REPONSE REGULATOR5 Form a Negative Feedback Loop within the Arabidopsis Circadian Clock

Circadian rhythms provide organisms with an adaptive advantage, allowing them to regulate physiological and developmental events so that they occur at the most appropriate time of day. In plants, as in other eukaryotes, multiple transcriptional feedback loops are central to clock function. In one such feedback loop, the Myb-like transcription factors CCA1 and LHY directly repress expression of the pseudoresponse regulator TOC1 by binding to an evening element (EE) in the TOC1 promoter. Another key regulatory circuit involves CCA1 and LHY and the TOC1 homologs PRR5, PRR7, and PRR9. Purification of EE–binding proteins from plant extracts followed by mass spectrometry led to the identification of RVE8, a homolog of CCA1 and LHY. Similar to these well-known clock genes, expression of RVE8 is circadian-regulated with a dawn phase of expression, and RVE8 binds specifically to the EE. However, whereas cca1 and lhy mutants have short period phenotypes and overexpression of either gene causes arrhythmia, rve8 mutants have long-period and RVE8-OX plants have short-period phenotypes. Light input to the clock is normal in rve8, but temperature compensation (a hallmark of circadian rhythms) is perturbed. RVE8 binds to the promoters of both TOC1 and PRR5 in the subjective afternoon, but surprisingly only PRR5 expression is perturbed by overexpression of RVE8. Together, our data indicate that RVE8 promotes expression of a subset of EE–containing clock genes towards the end of the subjective day and forms a negative feedback loop with PRR5. Thus RVE8 and its homologs CCA1 and LHY function close to the circadian oscillator but act via distinct molecular mechanisms

The elements of human cyclin D1 promoter and regulation involved

Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites such as AP-1, NF-қB, E2F, Oct-1, and so on. The extracellular signals functions through the signal transduction pathways converging at the binding sites to active or inhibit the promoter activity and regulate the cell cycle progression. Different signal transduction pathways regulate the promoter at different time to get the correct cell cycle switch. Disorder regulation or special extracellular stimuli can result in cell cycle out of control through the promoter activity regulation. Epigenetic modifications such as DNA methylation and histone acetylation may involved in cyclin D1 transcriptional regulation

Primary rat sertoli and interstitial cells exhibit a differential response to cadmium

Two cell types central to the support of spermatogenesis, the Sertoli cell and the interstitial (Leydig) cell, were isolated from the same cohort of young male rats and challenged with cadmium chloride to compare their susceptibility to the metal. Both cell types were cultured under similar conditions, and similar biochemical endpoints were chosen to minimize experimental variability. These endpoints include the uptake of 109 Cd, reduction of the vital tetrazolium dye MTT, incorporation of 3 H-leucine, change in heat-stable cadmium binding capacity, and production of lactate. Using these parameters, it was observed that the Sertoli cell cultures were adversely affected in a dose-and time-dependent manner, while the interstitial cell cultures, treated with identical concentrations of CdCl 2 , were less affected. The 72-hr LC 50 's for Sertoli cells and interstitial cells were 4.1 and 19.6 μM CdCl 2 , respectively. Thus, different cell populations within the same tissue may differ markedly in susceptibility to a toxicant. These in vitro data suggest that the Sertoli cell, in relation to the interstitium, is particularly sensitive to cadmium. Because the Sertoli cell provides functional support for the seminiferous epithelium, the differential sensitivity of this cell type may, in part, explain cadmium-induced testicular dysfunction, particularly at doses that leave the vascular epithelium intact.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42554/1/10565_2004_Article_BF00135027.pd

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine