scholarly journals Cellular and Molecular Heterogeneity Associated with Vessel Formation Processes

2018 ◽  
Vol 2018 ◽  
pp. 1-32 ◽  
Author(s):  
Pollyana Ribeiro Castro ◽  
Alan Sales Barbosa ◽  
Jousie Michel Pereira ◽  
Hedden Ranfley ◽  
Mariane Felipetto ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Postnatal Period ◽  
Molecular Heterogeneity ◽  
Molecular Signatures ◽  
Formation Processes ◽  
Vessel Formation ◽  
Mural Cells ◽  
Microvascular Cells ◽  
Interactive View ◽  
Complex Subject

The microvasculature heterogeneity is a complex subject in vascular biology. The difficulty of building a dynamic and interactive view among the microenvironments, the cellular and molecular heterogeneities, and the basic aspects of the vessel formation processes make the available knowledge largely fragmented. The neovascularisation processes, termed vasculogenesis, angiogenesis, arteriogenesis, and lymphangiogenesis, are important to the formation and proper functioning of organs and tissues both in the embryo and the postnatal period. These processes are intrinsically related to microvascular cells, such as endothelial and mural cells. These cells are able to adjust their activities in response to the metabolic and physiological requirements of the tissues, by displaying a broad plasticity that results in a significant cellular and molecular heterogeneity. In this review, we intend to approach the microvasculature heterogeneity in an integrated view considering the diversity of neovascularisation processes and the cellular and molecular heterogeneity that contribute to microcirculatory homeostasis. For that, we will cover their interactions in the different blood-organ barriers and discuss how they cooperate in an integrated regulatory network that is controlled by specific molecular signatures.

scholarly journals Identification of putative master regulators in rheumatoid arthritis synovial fibroblasts using gene expression data and network inference

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Naouel Zerrouk ◽  
Quentin Miagoux ◽  
Aurelien Dispot ◽  
Mohamed Elati ◽  
Anna Niarakis
Keyword(s):  
Rheumatoid Arthritis ◽  
Regulatory Network ◽  
Proteolytic Enzymes ◽  
The Body ◽  
Differentially Expressed ◽  
High Rate ◽  
Systemic Autoimmune Disease ◽  
Phenotypic Traits ◽  
Molecular Signatures ◽  
Master Regulators

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects the synovial joints of the body. Rheumatoid arthritis fibroblast-like synoviocytes (RA FLS) are central players in the disease pathogenesis, as they are involved in the secretion of cytokines and proteolytic enzymes, exhibit invasive traits, high rate of self-proliferation and an apoptosis-resistant phenotype. We aim at characterizing transcription factors (TFs) that are master regulators in RA FLS and could potentially explain phenotypic traits. We make use of differentially expressed genes in synovial tissue from patients suffering from RA and osteoarthritis (OA) to infer a TF co-regulatory network, using dedicated software. The co-regulatory network serves as a reference to analyze microarray and single-cell RNA-seq data from isolated RA FLS. We identified five master regulators specific to RA FLS, namely BATF, POU2AF1, STAT1, LEF1 and IRF4. TF activity of the identified master regulators was also estimated with the use of two additional, independent software. The identified TFs contribute to the regulation of inflammation, proliferation and apoptosis, as indicated by the comparison of their differentially expressed target genes with hallmark molecular signatures derived from the Molecular Signatures Database (MSigDB). Our results show that TFs influence could be used to identify putative master regulators of phenotypic traits and suggest novel, druggable targets for experimental validation.

scholarly journals Probing DNA interactions with proteins using a single-molecule toolbox: inside the cell, in a test tube and in a computer

2015 ◽  
Vol 43 (2) ◽  
pp. 139-145 ◽  
Author(s):  
Adam J. M. Wollman ◽  
Helen Miller ◽  
Zhaokun Zhou ◽  
Mark C. Leake
Keyword(s):  
Single Molecule ◽  
Protein Interactions ◽  
Super Resolution ◽  
Magnetic Tweezers ◽  
In Vivo Studies ◽  
Live Cells ◽  
Molecular Heterogeneity ◽  
Molecular Signatures

DNA-interacting proteins have roles in multiple processes, many operating as molecular machines which undergo dynamic meta-stable transitions to bring about their biological function. To fully understand this molecular heterogeneity, DNA and the proteins that bind to it must ideally be interrogated at a single molecule level in their native in vivo environments, in a time-resolved manner, fast enough to sample the molecular transitions across the free-energy landscape. Progress has been made over the past decade in utilizing cutting-edge tools of the physical sciences to address challenging biological questions concerning the function and modes of action of several different proteins which bind to DNA. These physiologically relevant assays are technically challenging but can be complemented by powerful and often more tractable in vitro experiments which confer advantages of the chemical environment with enhanced detection signal-to-noise of molecular signatures and transition events. In the present paper, we discuss a range of techniques we have developed to monitor DNA–protein interactions in vivo, in vitro and in silico. These include bespoke single-molecule fluorescence microscopy techniques to elucidate the architecture and dynamics of the bacterial replisome and the structural maintenance of bacterial chromosomes, as well as new computational tools to extract single-molecule molecular signatures from live cells to monitor stoichiometry, spatial localization and mobility in living cells. We also discuss recent developments from our laboratory made in vitro, complementing these in vivo studies, which combine optical and magnetic tweezers to manipulate and image single molecules of DNA, with and without bound protein, in a new super-resolution fluorescence microscope.

scholarly journals Parathyroid Tumors: Molecular Signatures

2021 ◽  
Vol 22 (20) ◽  
pp. 11206
Author(s):  
Francesca Marini ◽  
Francesca Giusti ◽  
Teresa Iantomasi ◽  
Maria Luisa Brandi
Keyword(s):  
Current Knowledge ◽  
Gene Mutations ◽  
Molecular Heterogeneity ◽  
Molecular Signatures ◽  
Epigenetic Changes ◽  
Parathyroid Tumor ◽  
Diagnostic Biomarkers ◽  
Tumor Subtypes ◽  
Parathyroid Tumors ◽  
Parathyroid Adenomas

Parathyroid tumors are rare endocrine neoplasms affecting 0.1–0.3% of the general population, including benign parathyroid adenomas (PAs; about 98% of cases), intermediate atypical parathyroid adenomas (aPAs; 1.2–1.3% of cases) and malignant metastatic parathyroid carcinomas (PCs; less than 1% of cases). These tumors are characterized by a variable spectrum of clinical phenotypes and an elevated cellular, histological and molecular heterogeneity that make it difficult to pre-operatively distinguish PAs, aPAs and PCs. Thorough knowledge of genetic, epigenetic, and molecular signatures, which characterize different parathyroid tumor subtypes and drive different tumorigeneses, is a key step to identify potential diagnostic biomarkers able to distinguish among different parathyroid neoplastic types, as well as provide novel therapeutic targets and strategies for these rare neoplasms, which are still a clinical and therapeutic challenge. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of different clinical types of parathyroid tumors, both in familial and sporadic forms of these endocrine neoplasms.

scholarly journals Molecular signatures for inflammation vary across cancer types and correlate significantly with tumor stage, gender and vital status of patients

2019 ◽  
Author(s):  
Alexandra R. So ◽  
Jeong Min Si ◽  
David Lopez ◽  
Matteo Pellegrini
Keyword(s):  
Expression Profiles ◽  
Molecular Classification ◽  
Classification Systems ◽  
Cancer Classification ◽  
P Value ◽  
Molecular Heterogeneity ◽  
Molecular Signatures ◽  
Systematic Analysis ◽  
Vital Status ◽  
Cancer Types

AbstractCancer affects millions of individuals worldwide. One shortcoming of traditional cancer classification systems is that, even for tumors affecting a single organ, there is significant molecular heterogeneity. Precise molecular classification of tumors could be beneficial in personalizing patients’ therapy and predicting prognosis. To this end, here we propose to use molecular signatures to further refine cancer classification. Molecular signatures are collections of genes characterizing particular cell types, tissues or disease. Signatures can be used to interpret expression profiles from heterogeneous samples. Large collections of gene signatures have previously been cataloged in the MSigDB database. We have developed a web-based Signature Visualization Tool (SaVanT) to display signature scores in user-generated expression data. Here we have undertaken a systematic analysis of correlations between inflammatory signatures and cancer samples, to test whether inflammation can differentiate cancer types. Inflammatory response signatures were obtained from MsigDB and SaVanT and a signature score was computed for samples associated with 7 different cancer types. We first identified types of cancers that had high inflammation levels as measured by these signatures. The correlation between signature scores and metadata of these patients (gender, age at initial cancer diagnosis, cancer stage, and vital status) was then computed. We sought to evaluate correlations between inflammation with other clinical parameters and identified four cancer types that had statistically significant association (p-value < 0.05) with at least one clinical characteristic: pancreas adenocarcinoma (PAAD), cholangiocarcinoma (CHOL), kidney chromophobe (KICH), and uveal melanoma (UVM). These results may allow future studies to use these approaches to further refine cancer subtyping and ultimately treatment.

I Like Her, Because I Like Myself: Self-Evaluation as a Source of Interpersonal Attitudes

2003 ◽  
Vol 50 (4) ◽  
pp. 239-246 ◽  
Author(s):  
Eva Walther ◽  
Claudia Trasselli
Keyword(s):  
Opposite Effect ◽  
Learning Phase ◽  
The Self ◽  
Attitude Formation ◽  
Formation Processes ◽  
False Feedback ◽  
Self Evaluation ◽  
Evaluation Group ◽  
Group A ◽  
The Difference

Abstract. Two experiments tested the hypothesis that self-evaluation can serve as a source of interpersonal attitudes. In the first study, self-evaluation was manipulated by means of false feedback. A subsequent learning phase demonstrated that the co-occurrence of the self with another individual influenced the evaluation of this previously neutral target. Whereas evaluative self-target similarity increased under conditions of negative self-evaluation, an opposite effect emerged in the positive self-evaluation group. A second study replicated these findings and showed that the difference between positive and negative self-evaluation conditions disappeared when a load manipulation was applied. The implications of self-evaluation for attitude formation processes are discussed.

Complex Subject : Simple Approach

2004 ◽  
Vol 49 (4) ◽  
pp. 401-403
Author(s):  
Richard B. Makover
Keyword(s):  
Simple Approach ◽  
Complex Subject

On Beginning to Become Dietitians

2014 ◽  
Vol 2 (1) ◽  
pp. 8
Author(s):  
Debbie MacLellan ◽  
Jacqui Gingras ◽  
Daphne Lordly ◽  
Jennifer Brady
Keyword(s):  
Identity Formation ◽  
Professional Socialization ◽  
Early Years ◽  
Formation Processes ◽  
Socialization Process ◽  
Complex Process ◽  
The Future

This paper explores beginning dietetic practitioners’ perspectives on the process of becoming dietetics professionals through the use of vignettes to illuminate the complex process of professional socialization.  Embedded in these vignettes are three themes related to the socialization process that occurs in the early years of dietetic practice: congruence, resilience, and relationships.  Our findings indicate that new dietitians struggle to develop their dietitian identity.  They feel unprepared for the relational and practice realities of the workplace and find the transition from dietetic intern to dietitian challenging.  They seek many ways to cope including seeking support from others and planning for the future but some consider leaving the profession.  It is important to understand the professional socialization and identity formation processes that occur during the early years of practice to ensure that dietitians feel prepared and supported as they begin their careers.

His Lordship's -ship and the King of Golfdom. Against a purely functional analysis of suffixhood

2010 ◽  
Vol 3 (1) ◽  
pp. 1-30 ◽  
Author(s):  
Heike Baeskow
Keyword(s):  
Functional Analysis ◽  
Conceptual Knowledge ◽  
Semantic Information ◽  
Word Formation ◽  
Distributed Morphology ◽  
Word Class ◽  
Formation Processes ◽  
Functional Elements ◽  
Grammatical Morphemes ◽  
Independent Model

For many decades there has been a consensus among linguists of various schools that derivational suffixes function not only to determine the word-class of the complex expressions they form, but also convey semantic information. The aspect of suffix-inherent meaning is ignored by representatives of a relatively new theoretical direction – Neo-Construction Grammar – who consider derivational suffixes to be either purely functional elements of the grammar or meaningless phonological realizations of abstract grammatical morphemes. The latter view is maintained by adherents of Distributed Morphology, who at the same time emphasize the importance of conceptual knowledge for derivational processes without attempting to define this aspect. The purpose of this study is first of all to provide support for the long-standing assumption that suffixes are inherently meaningful. The focus of interest is on the suffixes -ship, -dom and -hood. Data from Old English and Modern English (including neologisms) will show that these suffixes have developed rich arrays of meaning which cannot be structurally derived. Moreover, since conceptual knowledge is indeed an important factor for word-formation processes, a concrete, theory-independent model for the representation of the synchronically observable meaning components associated with -ship, -dom and -hood will be proposed.

A Prehistoric Ford near Rough Castle, Falkirk

2001 ◽  
Vol 23 (2) ◽  
pp. 91-103
Author(s):  
JAMIE HAMILTON ◽  
CIARA CLARKE ◽  
ANDREW DUNWELL ◽  
RICHARD TIPPING
Keyword(s):  
Coal Mining ◽  
Pollen Analysis ◽  
Site Formation ◽  
Site Formation Processes ◽  
Formation Processes ◽  
Radiocarbon Dates ◽  
Small Stream ◽  
Mining Project ◽  
First Millennium

This report presents the results of the excavation of a stone ford laid across the base of a small stream valley near Rough Castle, Falkirk. It was discovered during an opencast coal mining project. Radiocarbon dates and pollen analysis of deposits overlying the ford combine to indicate a date for its construction no later than the early first millennium cal BC. Interpreting this evidence was not straightforward and the report raises significant issues about site formation processes and the interpretation of radiocarbon and pollen evidence. The importance of these issues extends beyond the rarely investigated features such as fords and deserve a larger place in the archaeological literature.

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