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Chronic Intestinal Pseudo-Obstruction (CIPO): interplay between enteric nervous system, serotonin and mucosa-associated microbiota
Full text linkIntroduction: Chronic intestinal pseudo-obstruction (CIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the absence of lumen-occluding lesions. It results from an extremely severe impairment of propulsive motility. Serotonin (5-HT, a local mediator and neurotransmitter) release is linked to intestinal peristaltic and secretory reflexes. The intestinal microbiota and the enteric nervous system (ENS) interact and this results in effects on the synthesis of 5-HT, its release and the subsequent serotonin receptors’ activation. The interplay between ENS/5-HT and dysbiosis in CIPO remains largely unclear. The project aim was to assess correlations between gut microbiota and intestinal serotonin-related genes expression in CIPO pediatric patients. For this purpose, mucosa-associated microbiota (MAM) has been characterized, and changes in gastrointestinal (GI) serotonin pathway have been evaluated.
Material and Methods: We collected biopsies of the colon, the ileum and the duodenum from 7 pediatric CIPO patients and 7 age-/sex-matched healthy controls at Cesare Arrigo Childrens’ Hospital (Alessandria, Italy). After DNA extraction, the MAM was assessed by next generation sequencing (NGS) of the V3-V4 region of the bacterial RNA 16s, on an Illumina Miseq platform. The expression of genes implicated in serotoninergic pathway (TPH1, SLC6A4, 5-HTR3 and 5-HTR4) was established by qPCR, after total RNA extraction from the same tissue samples. Correlation analyses were performed to highlight relationships between MAM and the expression of genes linked to the production (TPH1), transport (SLC6A4) and reception (5-HTR3, 5-HTR4) of 5-HT in CIPO patients. Results: Our results revealed a colonic MAM different in its composition and biodiversity with respect to controls. Network analysis evidenced, in CIPO patients, a microbial ecosystem with fewer species, less connected, and with a greater number of non-synergistic
relationships compared to controls. qPCR analysis results revealed alterations, a general a decrease, in the expression of serotonin-related genes for CIPO patients when compared to controls. Correlation analysis between the expression of serotonin-related genes and the colon-associated gut microbiota showed some significant but weak correlations, probably due to the low number of samples analyzed. Discussion and conclusion: Results showed, for the first time in CIPO patients, a specific colon-associated MAM, an altered expression of genes related to intestinal serotonin pathway and significant, but weak, interconnections between the microbiota and serotonin-related
genes expression, indicating that alterations in this pathway seem to be related to the altered MAM. A possible malfunctioning in the 5-HT pathway, maybe linked to or triggered by an altered microbiota, could be a mechanism underlying the intestinal motility disorder in CIPO patients. Our results could also represent the first step to design a new therapy targeting the microbiota or targeting the serotonin pathways, improving treatment outcomes and quality of life for CIPO patients
Development of phenotypic indexes for the description of morphological injury in breast cancer cell mitochondria.
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Development of phenotypic indexes for the description of morphological injury in breast cancer cell mitochondria.
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Sub-category:
Tumor/Cell Biology
Category:
Tumor Biology
Meeting:
2009 ASCO Annual Meeting
Session Type and Session Title:
This abstract will not be presented at the 2009 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract No:
e22055
Citation:
J Clin Oncol 27, 2009 (suppl; abstr e22055)
Author(s):
L. Putignani, S. Raffa, R. Pescosolido, F. Signore, D. Menichella, R. Boldrini, M. Torrisi, P. Grammatico; Bambino Gesù, Rome, Italy; S. Andrea Hospital, Rome, Italy; S. Camillo-Forlanini Hospital, Rome, Italy; Bambino Gesù Hospital, Rome, Italy; S. Andrea Hospital, University Sapienza, Rome, Italy
Abstract Disclosures
Faculty and Discussant Disclosures
Annual Meeting Planning Committee Disclosures
2009 Annual Meeting Proceedings Part I Errata
Abstract:
Background: Mitochondriopathy has been recently rekindled as new cancer theory. We report on structural damage of breast-infiltrating ductal carcinoma (IDC) mitochondria characterised by reduced expression levels of the oxidative phosphorylation system (OXPHOS). Methods: Mitochondria from HMC-1 (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures, traced by Mitotracker, were assayed for OXPHOS expression levels using cryo-immunoelectron microscopy (CIEM) quantitative labelling and fluorescence immunolabelling on unfractionated HMC-1 and HEMC cells. Convolution degeneration was established by transmission electron microscopy (TEM). Twenty different cell sections for both HMC-1 and HEMC cells, including 65 and 72 mitochondria, respectively, were randomly recorded and quantitatively analyzed for the percentage of area occupied by intact cristae to provide a grading of mitochondrial damage (cristae loss index). Results: Depressed expression levels were detected for all HMC-1 OXPHOS complexes by CIEM. Normalized labelling density (HEMC/HMC-1), expressed as colloidal gold particles/mitochondrial area (ρ) provided the following values: 1.77 for the NADH-ubiquinone oxidoreductase complex I NDUFS3; 1.86 for the succinate- dehydrogenase complex II SDH-B protein; 1.63 for the ubiquinol cytochrome c reductase complex III UQCRC2; 4.88 and 1.58 for the cytochrome-oxidase complex IV (CO) subunit I and IV, respectively; 2.70 for the ATP-synthase complex V F1β protein. Fluorescence immunolabelling confirmed CIEM quantitative data. MitoTracker's co-staining showed altered membrane potential and permeability. Injury grading was categorised assigning three levels of morphological damage: i) severe, ii) moderate, iii) slight, corresponding to 0 % (6.2 % and 1.4 % for HMC-1 and HMEC, respectively), 1-50 % (21.5 % and 2.8 % for HMC-1 and HMEC, respectively) and 51-75 % (44.6 % and 15.3 % for HMC-1 and HMEC, respectively) of area occupied by intact cristae (p<0.0001, χ2 Test). The entire HMC-1 mitochondrial damage resulted 3.7 times higher than that observed for HMEC cells (72.3HMC-1 %/19.5HMEC %). Conclusions: New phenotypic harm indexes for IDC cell mitochondria might provide new hallmarks in breast cancer cell biology
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Identification of clinically relevant yeasts by DNA sequence analysis of the D2 variable region of the 25-28S rRNA gene
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koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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