Using digital social market applications to incentivise active travel: Empirical analysis of a smart city initiative

Information and communication technologies (ICTs), such as mobile communication networks, and behaviour-based approaches for citizen engagement play a key role in making future cities sustainable and tackling persistent problems in high-density urban areas. In the context of Sharing Cities, an EU-funded programme aiming to deliver smart city solutions in areas such as citizen participation and infrastructure improvements of buildings and mobility, a prominent intervention has been the deployment and monitoring of a Digital Social Market (DSM) tool in Milan (Italy). The DSM allows cities to engage with residents and encourage sustainable behaviours by offering non-monetary rewards. This paper aims to evaluate the effectiveness of the DSM approach to promote active travel (cycling and walking) by analysing the data collected through the app as well as through participant surveys. Our model results show that a broader engagement with the DSM app (number of claps to posts, number of posts made, non-monetary rewards earned by participating in non-travel events) is positively correlated with the monitored level of active travel. Lifestyles, attitudes, and social influence also explain the variability in cycling and walking. This highlights the importance of investigating these factors when replicating such initiatives on a large scale

Differences in Disease Severity but Similar Telomere Lengths in Genetic Subgroups of Patients with Telomerase and Shelterin Mutations

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Discovery of Novel Biomarkers by Microarray Analysis of Peripheral Blood Mononuclear Cell Gene Expression in Benzene-Exposed Workers

Benzene is an industrial chemical and component of gasoline that is an established cause of leukemia. To better understand the risk benzene poses, we examined the effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression in a population of shoe-factory workers with well-characterized occupational exposures using microarrays and real-time polymerase chain reaction (PCR). PBMC RNA was stabilized in the field and analyzed using a comprehensive human array, the U133A/B Affymetrix GeneChip set. A matched analysis of six exposed–control pairs was performed. A combination of robust multiarray analysis and ordering of genes using paired t-statistics, along with bootstrapping to control for a 5% familywise error rate, was used to identify differentially expressed genes in a global analysis. This resulted in a set of 29 known genes being identified that were highly likely to be differentially expressed. We also repeated these analyses on a smaller subset of 508 cytokine probe sets and found that the expression of 19 known cytokine genes was significantly different between the exposed and the control subjects. Six genes were selected for confirmation by real-time PCR, and of these, CXCL16, ZNF331, JUN, and PF4 were the most significantly affected by benzene exposure, a finding that was confirmed in a larger data set from 28 subjects. The altered expression was not caused by changes in the makeup of the PBMC fraction. Thus, microarray analysis along with real-time PCR confirmation reveals that altered expressions of CXCL16, ZNF331, JUN, and PF4 are potential biomarkers of benzene exposure

CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells

INTRODUCTION: Breast cancer is thought to arise in mammary epithelial stem cells. There is, therefore, a large amount of interest in identifying these cells. The breast is a complex tissue consisting of two epithelial layers (an outer myoepithelial/basal layer and an inner luminal epithelial layer) as well as a large non-epithelial component (fibroblasts, endothelial cells, lymphocytes, adipocytes, neurons and myocytes). The definitive identification of a mammary epithelial stem cell population is critically dependent on its purity. To date, this has been hampered by the lack of suitable markers to separate out the two epithelial layers, and to remove contaminating non-epithelial cells. METHODS: Mouse mammary glands were dissociated and stained with CD24. Cells were sorted into separate populations based on CD24 expression and assessed for luminal epithelial and myoepithelial/basal markers by direct fluorescent microscopy and real time PCR. The stem/progenitor potential of these cell populations was assessed in vivo by cleared mammary fat pad transplantation. RESULTS: Three populations of CD24 expressing cells were identified: CD24(Negative), CD24(Low )and CD24(High). Staining of these cells with cytokeratin markers revealed that these populations correspond to non-epithelial, myoepithelial/basal and luminal epithelial cells, respectively. Cell identities were confirmed by quantitative PCR. Cleared mammary fat pad transplantation of these cell populations revealed that extensive mammary fat pad repopulation capacity segregates with the CD24(Low )cells, whilst CD24(High )cells have limited repopulation capacity. CONCLUSION: Differential staining of mammary epithelial cells for CD24 can be used to simultaneously isolate pure populations of non-epithelial, myoepithelial/basal and luminal epithelial cells. Furthermore, mammary fat pad repopulation capacity is enriched in the CD24(Low )population. As separation is achieved using a single marker, it will be possible to incorporate additional markers to further subdivide these populations. This will considerably facilitate the further analysis of mammary epithelial subpopulations, whilst ensuring high purity, which is key for understanding mammary epithelial stem cells in normal tissue biology and carcinogenesis

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Transgenic CHD1L Expression in Mouse Induces Spontaneous Tumors

Background: Amplification of 1q21 is the most frequent genetic alteration in hepatocellular carcinoma (HCC), which was detected in 58-78% of primary HCC cases by comparative genomic hybridization (CGH). Using chromosome microdissection/ hybrid selection approach we recently isolated a candidate oncogene CHD1L from 1q21 region. Our previous study has demonstrated that CHD1L had strong oncogenic ability, which could be effectively suppressed by siRNA against CHD1L. The molecular mechanism of CHD1L in tumorigenesis has been associated with its role in promoting cell proliferation. Methodology/Principal Findings: To further investigate the in vivo oncogenic role of CHD1L, CHD1L ubiquitous-expression transgenic mouse model was generated. Spontaneous tumor formations were found in 10/41 (24.4%) transgenic mice, including 4 HCCs, but not in their 39 wild-type littermates. In addition, alcohol intoxication was used to induce hepatocyte pathological lesions and results found that overexpression of CHD1L in hepatocytes could promote tumor susceptibility in CHD1L-transgenic mice. To address the mechanism of CHD1L in promoting cell proliferation, DNA content between CHD1Ltransgenic and wildtype mouse embryo fibroblasts (MEFs) was compared by flow cytometry. Flow cytometry results found that CHD1L could facilitate DNA synthesis and G1/ S transition through the up-regulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, and CDK4, and down-regulation of Rb, p27Kip1, and p53. Conclusion/Significance: Taken together, our data strongly support that CHD1L is a novel oncogene and plays an important role in HCC pathogenesis. © 2009 Chen et al.published_or_final_versio

Diammonium Glycyrrhizinate Upregulates PGC-1α and Protects against Aβ1–42-Induced Neurotoxicity

Mitochondrial dysfunction is a hallmark of beta-amyloid (Aβ)-induced neurotoxicity in Alzheimer's disease (AD), and is considered an early event in AD pathology. Diammonium glycyrrhizinate (DG), the salt form of Glycyrrhizin, is known for its anti-inflammatory effects, resistance to biologic oxidation and membranous protection. In the present study, the neuroprotective effects of DG on Aβ1–42-induced toxicity and its potential mechanisms in primary cortical neurons were investigated. Exposure of neurons to 2 µM Aβ1–42 resulted in significant viability loss and cell apoptosis. Accumulation of reactive oxygen species (ROS), decreased mitochondrial membrane potential, and activation of caspase-9 and caspase-3 were also observed after Aβ1–42 exposure. All these effects induced by Aβ1–42 were markedly reversed by DG treatment. In addition, DG could alleviate lipid peroxidation and partially restore the mitochondrial function in Aβ1–42-induced AD mice. DG also significantly increased the PGC-1α expression in vivo and in vitro, while knocking down PGC-1α partially blocked the protective effects, which indicated that PGC-1α contributed to the neuroprotective effects of DG. Furthermore, DG significantly decreased the escape latency and search distance and increased the target crossing times of Aβ1–42-induced AD mice in the Morris water maze test. Therefore, these results demonstrated that DG could attenuate Aβ1–42-induced neuronal injury by preventing mitochondrial dysfunction and oxidative stress and improved cognitive impairment in Aβ1–42-induced AD mice, indicating that DG exerted potential beneficial effects on AD

The regulatory mechanism of fungal elicitor-induced secondary metabolite biosynthesis in medical plants.

A wide range of external stress stimuli trigger plant cells to undergo complex network of reactions that ultimately lead to the synthesis and accumulation of secondary metabolites. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Throughout evolution, endophytic fungi, an important constituent in the environment of medicinal plants, have known to form long-term stable and mutually beneficial symbiosis with medicinal plants. The endophytic fungal elicitor can rapidly and specifically induce the expression of specific genes in medicinal plants which can result in the activation of a series of specific secondary metabolic pathways resulting in the significant accumulation of active ingredients. Here we summarize the progress made on the mechanisms of fungal elicitor including elicitor signal recognition, signal transduction, gene expression and activation of the key enzymes and its application. This review provides guidance on studies which may be conducted to promote the efficient synthesis and accumulation of active ingredients by the endogenous fungal elicitor in medicinal plant cells, and provides new ideas and methods of studying the regulation of secondary metabolism in medicinal plants