A century of the evolution of the urban system in Brazil

In this paper, we study the hitherto unexplored evolution of the size distribution of 185 urban areas in Brazil between 1907 and 2008. We find that the power law parameter of the size distribution of the 100 largest urban areas increases from 0.63 in 1907 to 0.89 in 2008, which confirms an agglomeration process in which the size distribution has become more unequal. A panel fixed effects model pooling the same range of urban size distributions provides a power law parameter equal to 0.53, smaller than those from cross-sectional estimation. Clearly, Zipf’s Law is rejected. The lognormal distribution fits the city size distribution quite well until the 1940s, but since then applies to small and medium size cities only. These results are consistent with our understanding of historical-political and socio-economic processes that have shaped the development of Brazilian cities

Agglomeration externalities and 1981-2006 regional growth in Brazil

This paper focuses on manufacturing employment growth across the 26 states of Brazil. We employ the Glaeser et al. (1992) approach to identify the role played by knowledge externalities in growth and convergence. To assess robustness of the results, we compare cross-section models, dynamic panel models and pooled-periods fixed-effect models. We find that cross-section models confirm the positive impact of Porter’s and Jacobs’ competition externalities on growth, whereas dynamic panel models and pooled-periods fixed-effect models are consistent with the predictions of Marshall-Arrow-Romer and Porter regarding the role of specialisation in manufacturing vis-à-vis other employment. The results provide new insights into the rapid growth since 1981 in particularly the North and Centre West of Brazil

The anti-proliferative Effects of enterolactone in prostate cancer cells: evidence for the role of DNA licencing genes, mi-R106b cluster expression, and PTEN dosage

The mammalian lignan, enterolactone, has been shown to reduce the proliferation of the earlier stages of prostate cancer at physiological concentrations in vitro. However, efficacy in the later stages of the disease occurs at concentrations difficult to achieve through dietary modification. We have therefore investigated what concentration(s) of enterolactone can restrict proliferation in multiple stages of prostate cancer using an in vitro model system of prostate disease. We determined that enterolactone at 20 μM significantly restricted the proliferation of mid and late stage models of prostate disease. These effects were strongly associated with changes in the expression of the DNA licencing genes (GMNN, CDT1, MCM2 and 7), in reduced expression of the miR-106b cluster (miR-106b, miR-93, and miR-25), and in increased expression of the PTEN tumour suppressor gene. We have shown anti-proliferative effects of enterolactone in earlier stages of prostate disease than previously reported and that these effects are mediated, in part, by microRNA-mediated regulation

Expression profiling indicating low selenium-sensitive microRNA levels linked to cell cycle and cell stress response pathways in the CaCo-2 cell line

Se is an essential micronutrient for human health, and fluctuations in Se levels and the potential cellular dysfunction associated with it may increase the risk for disease. Although Se has been shown to influence several biological pathways important in health, little is known about the effect of Se on the expression of microRNA (miRNA) molecules regulating these pathways. To explore the potential role of Se-sensitive miRNA in regulating pathways linked with colon cancer, we profiled the expression of 800 miRNA in the CaCo-2 human adenocarcinoma cell line in response to a low-Se (72 h at <40 nm) environment using nCounter direct quantification. These data were then examined using a range of in silico databases to identify experimentally validated miRNA-mRNA interactions and the biological pathways involved. We identified ten Se-sensitive miRNA (hsa-miR-93-5p, hsa-miR-106a-5p, hsa-miR-205-5p, hsa-miR-200c-3p, hsa-miR-99b-5p, hsa-miR-302d-3p, hsa-miR-373-3p, hsa-miR-483-3p, hsa-miR-512-5p and hsa-miR-4454), which regulate 3588 mRNA in key pathways such as the cell cycle, the cellular response to stress, and the canonical Wnt/β-catenin, p53 and ERK/MAPK signalling pathways. Our data show that the effects of low Se on biological pathways may, in part, be due to these ten Se-sensitive miRNA. Dysregulation of the cell cycle and of the stress response pathways due to low Se may influence key genes involved in carcinogenesis

Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer

BACKGROUND: There is a probable association between consumption of fruit and vegetables and reduced risk of cancer, particularly cancer of the digestive tract. This anti-cancer activity has been attributed in part to anti-oxidants present in these foods. Raspberries in particular are a rich source of the anti-oxidant compounds, such as polyphenols, anthocyanins and ellagitannins. METHODS: A "colon-available" raspberry extract (CARE) was prepared that contained phytochemicals surviving a digestion procedure that mimicked the physiochemical conditions of the upper gastrointestinal tract. The polyphenolic-rich extract was assessed for anti-cancer properties in a series of in vitro systems that model important stages of colon carcinogenesis, initiation, promotion and invasion. RESULTS: The phytochemical composition of CARE was monitored using liquid chromatography mass spectrometry. The colon-available raspberry extract was reduced in anthocyanins and ellagitannins compared to the original raspberry juice but enriched in other polyphenols and polyphenol breakdown products that were more stable to gastrointestinal digestion. Initiation – CARE caused significant protective effects against DNA damage induced by hydrogen peroxide in HT29 colon cancer cells measured using single cell microgelelectrophoresis. Promotion – CARE significantly decreased the population of HT29 cells in the G(1 )phase of the cell cycle, effectively reducing the number of cells entering the cell cycle. However, CARE had no effect on epithelial integrity (barrier function) assessed by recording the trans-epithelial resistance (TER) of CACO-2 cell monolayers. Invasion – CARE caused significant inhibition of HT115 colon cancer cell invasion using the matrigel invasion assay. CONCLUSION: The results indicate that raspberry phytochemicals likely to reach the colon are capable of inhibiting several important stages in colon carcinogenesis in vitro

Identifying Priority and “Bright-Spot” Counties for Diabetes Preventive Care in Appalachia: An Exploratory Analysis

Introduction: Type 2 diabetes mellitus (T2DM) prevalence and mortality in Appalachian counties is substantially higher when compared to non-Appalachian counties, although there is significant variation within Appalachia. Purpose: The objectives of this research were to identify low-performing (priority) and high-performing (bright spot) counties with respect to improving T2DM preventive care. Methods: Using data from the Centers for Medicare and Medicaid (CMS), the Dartmouth Atlas of Health Care, and the Appalachia Regional Commission, conditional maps were created using county-level estimates for T2DM prevalence, mortality, and annual hemoglobin A1c (HbA1c) testing rates. Priority counties were identified using the following criteria: top 33rd percentile for T2DM mortality; top 33rd percentile for T2DM prevalence; bottom 50th percentile for A1c testing rates. Bright spot counties were identified as counties in the bottom 33rd percentile for T2DM mortality, the top 33rd percentile for T2DM prevalence; and the top 50th percentile for HbA1c testing rates. Results: Forty-one priority counties were identified (those with high T2DM mortality, high T2DM prevalence, and low HbA1c testing rates), which were located primarily in Central and North Central Appalachia; and 17 bright spot counties were identified (high T2DM prevalence, low T2DM mortality, and high HbA1c testing rates), which were scattered throughout Appalachia. Eight of the 17 bright spot counties were adjacent to priority counties. Implications: By employing conditional mapping to T2DM, multiple variables can be summarized into a single, easily interpretable map. This could be valuable for T2DM-prevention programs seeking to prioritize diagnostic and intervention resources for the management of T2DM in Appalachia

Evidence synthesis for constructing directed acyclic graphs (ESC-DAGs): a novel and systematic method for building directed acyclic graphs

Background: Directed acyclic graphs (DAGs) are popular tools for identifying appropriate adjustment strategies for epidemiological analysis. However, a lack of direction on how to build them is problematic. As a solution, we propose using a combination of evidence synthesis strategies and causal inference principles to integrate the DAG-building exercise within the review stages of research projects. We demonstrate this idea by introducing a novel protocol: ‘Evidence Synthesis for Constructing Directed Acyclic Graphs’ (ESC-DAGs)’.\ud Methods: ESC-DAGs operates on empirical studies identified by a literature search, ideally a novel systematic review or review of systematic reviews. It involves three key stages: (i) the conclusions of each study are ‘mapped’ into a DAG; (ii) the causal structures in these DAGs are systematically assessed using several causal inference principles and are corrected accordingly; (iii) the resulting DAGs are then synthesised into one or more ‘integrated DAGs’. This demonstration article didactically applies ESC-DAGs to the literature on parental influences on offspring alcohol use during adolescence. Conclusions: ESC-DAGs is a practical, systematic and transparent approach for developing DAGs from background knowledge. These DAGs can then direct primary data analysis and DAG-based sensitivity analysis. ESC-DAGs has a modular design to allow researchers who are experienced DAG users to both use and improve upon the approach. It is also accessible to researchers with limited experience of DAGs or evidence synthesis

Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation

<p>Abstract</p> <p>Background</p> <p>Intestinal barrier function is important for preserving health, as a compromised barrier allows antigen entry and can induce inflammatory diseases. Probiotic bacteria can play a role in enhancing intestinal barrier function; however, the mechanisms are not fully understood. Existing studies have focused on the ability of probiotics to prevent alterations to tight junctions in disease models, and have been restricted to a few tight junction bridging proteins. No studies have previously investigated the effect of probiotic bacteria on healthy intestinal epithelial cell genes involved in the whole tight junction signalling pathway, including those encoding for bridging, plaque and dual location tight junction proteins. Alteration of tight junction signalling in healthy humans is a potential mechanism that could lead to the strengthening of the intestinal barrier, resulting in limiting the ability of antigens to enter the body and potentially triggering undesirable immune responses.</p> <p>Results</p> <p>The effect of <it>Lactobacillus plantarum </it>MB452 on tight junction integrity was determined by measuring trans-epithelial electrical resistance (TEER) across Caco-2 cell layers. <it>L. plantarum </it>MB452 caused a dose-dependent TEER increase across Caco-2 cell monolayers compared to control medium. Gene expression was compared in Caco-2 cells untreated or treated with <it>L. plantarum </it>MB452 for 10 hours. Caco-2 cell RNA was hybridised to human oligonucleotide arrays. Data was analysed using linear models and differently expressed genes were examined using pathway analysis tools. Nineteen tight junction-related genes had altered expression levels in response to <it>L. plantarum </it>MB452 (modified-P < 0.05, fold-change > 1.2), including those encoding occludin and its associated plaque proteins that anchor it to the cytoskeleton. <it>L. plantarum </it>MB452 also caused changes in tubulin and proteasome gene expression levels which may be linked to intestinal barrier function. Caco-2 tight junctions were visualised by fluorescent microscopy of immuno-stained occludin, zona occludens (ZO)-1, ZO-2 and cingulin. Caco-2 cells treated with <it>L. plantarum </it>MB452 had higher intensity fluorescence of each of the four tight junction proteins compared to untreated controls.</p> <p>Conclusions</p> <p>This research indicates that enhancing the expression of genes involved in tight junction signalling is a possible mechanism by which <it>L. plantarum </it>MB452 improves intestinal barrier function.</p