503 research outputs found

    Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice.

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    Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin in human colorectal cancer cells, we found that E-cadherin, a protein that regulates cell-cell adhesion, epithelial-mesenchymal transition and metastasis, was almost completely lost in Dcn(-/-) mouse intestine, and loss of decorin and E-cadherin accelerated colon cancer cell growth and invasion in Dcn(-/-) mice. However, increasing decorin expression in colorectal cancer cells attenuated cancer cell malignancy, including inhibition of cancer cell proliferation, promotion of apoptosis and importantly, attenuation of cancer cell migration. All these changes were linked to the regulation of E-cadherin by decorin. Moreover, overexpression of decorin upregulated E-cadherin through increasing of E-cadherin protein stability as E-cadherin messenger RNA and promoter activity were not affected. Co-immunoprecipitation assay showed a physical binding between decorin and E-cadherin proteins. Taken together, our results provide direct evidence that decorin-mediated inhibition of colorectal cancer growth and migration are through the interaction with and stabilization of E-cadherin

    Transcriptome profiles of strawberry (Fragaria vesca) fruit interacting with Botrytis cinerea at different ripening stages

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    Gray mold caused by Botrytis cinerea is a major cause of economic losses in strawberry fruit production, limiting fruit shelf life and commercialization. When the fungus infects Fragaria × ananassa strawberry at flowering or unripe fruit stages, symptoms develop after an extended latent phase on ripe fruits before or after harvesting. To elucidate the growth kinetics of B. cinerea on flower/fruit and the molecular responses associated with low susceptibility of unripe fruit stages, woodland strawberry Fragaria vesca flowers and fruits, at unripe white and ripe red stages, were inoculated with B. cinerea. Quantification of fungal genomic DNA within 72 h postinoculation (hpi) showed limited fungal growth on open flower and white fruit, while on red fruit, the growth was exponential starting from 24 hpi and sporulation was observed within 48 hpi. RNA sequencing applied to white and red fruit at 24 hpi showed that a total of 2,141 genes (12.5% of the total expressed genes) were differentially expressed due to B. cinerea infection. A broad transcriptional reprogramming was observed in both unripe and ripe fruits, involving in particular receptor and signaling, secondary metabolites, and defense response pathways. Membrane-localized receptor-like kinases and nucleotide-binding site leucine-rich repeat genes were predominant in the surveillance system of the fruits, most of them being downregulated in white fruits and upregulated in red fruits. In general, unripe fruits exhibited a stronger defense response than red fruits. Genes encoding for pathogenesis-related proteins and flavonoid polyphenols as well as genes involved in cell-wall strengthening were upregulated, while cell-softening genes appeared to be switched off. As a result, B. cinerea remained quiescent in white fruits, while it was able to colonize ripe red fruit

    Efficient Conversion of Astrocytes to Functional Midbrain Dopaminergic Neurons Using a Single Polycistronic Vector

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    Direct cellular reprogramming is a powerful new tool for regenerative medicine. In efforts to understand and treat Parkinson's Disease (PD), which is marked by the degeneration of dopaminergic neurons in the midbrain, direct reprogramming provides a valuable new source of these cells. Astrocytes, the most plentiful cells in the central nervous system, are an ideal starting population for the direct generation of dopaminergic neurons. In addition to their potential utility in cell replacement therapies for PD or in modeling the disease in vitro, astrocyte-derived dopaminergic neurons offer the prospect of direct in vivo reprogramming within the brain. As a first step toward this goal, we report the reprogramming of astrocytes to dopaminergic neurons using three transcription factors – ASCL1, LMX1B, and NURR1 – delivered in a single polycistronic lentiviral vector. The process is efficient, with 18.2±1.5% of cells expressing markers of dopaminergic neurons after two weeks. The neurons exhibit expression profiles and electrophysiological characteristics consistent with midbrain dopaminergic neurons, notably including spontaneous pacemaking activity, stimulated release of dopamine, and calcium oscillations. The present study is the first demonstration that a single vector can mediate reprogramming to dopaminergic neurons, and indicates that astrocytes are an ideal starting population for the direct generation of dopaminergic neurons

    Dangers of Catcalling: Exploring the Lived Experiences of Women Catcalled in Quezon City

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    Despite being a women's problem for a long time, catcalling has recently attracted lawmakers' attention. In 2019, the Philippine government enacted Republic Act 11313, or the Safe Spaces Act, which prohibits and punishes gender-based sexual harassment. However, despite the existence of the law, catcalling continues to be rampant. This study aims to explore the experiences of women in Quezon City who have been subjected to catcalling and to provide answers regarding the effects of catcalling on the victims, the locations where catcalling is most prevalent, the most common perpetrators, and the victim's views on the Safe Spaces Act. This research uses a qualitative descriptive approach. Purposive sampling was used to select respondents, and respondents were interviewed using an interview guide to gather information. The findings indicate that women are most vulnerable to catcalling in public spaces, and the perpetrators are strangers or bystanders. Victims went through mental, emotional, and behavioral changes after the incident. Moreover, not all victims think that the law effectively addresses the problem because catcalling is still prevalent, and public awareness campaigns are lacking

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Genetic Evidence for Hybrid Trait Speciation in Heliconius Butterflies

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    Homoploid hybrid speciation is the formation of a new hybrid species without change in chromosome number. So far, there has been a lack of direct molecular evidence for hybridization generating novel traits directly involved in animal speciation. Heliconius butterflies exhibit bright aposematic color patterns that also act as cues in assortative mating. Heliconius heurippa has been proposed as a hybrid species, and its color pattern can be recreated by introgression of the H. m. melpomene red band into the genetic background of the yellow banded H. cydno cordula. This hybrid color pattern is also involved in mate choice and leads to reproductive isolation between H. heurippa and its close relatives. Here, we provide molecular evidence for adaptive introgression by sequencing genes across the Heliconius red band locus and comparing them to unlinked wing patterning genes in H. melpomene, H. cydno, and H. heurippa. 670 SNPs distributed among 29 unlinked coding genes (25,847bp) showed H. heurippa was related to H. c. cordula or the three species were intermixed. In contrast, among 344 SNPs distributed among 13 genes in the red band region (18,629bp), most showed H. heurippa related with H. c. cordula, but a block of around 6,5kb located in the 3′ of a putative kinesin gene grouped H. heurippa with H. m. melpomene, supporting the hybrid introgression hypothesis. Genealogical reconstruction showed that this introgression occurred after divergence of the parental species, perhaps around 0.43Mya. Expression of the kinesin gene is spatially restricted to the distal region of the forewing, suggesting a mechanism for pattern regulation. This gene therefore constitutes the first molecular evidence for adaptive introgression during hybrid speciation and is the first clear candidate for a Heliconius wing patterning locus
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