scholarly journals E-cadherin Beyond Structure: A Signaling Hub in Colon Homeostasis and Disease

2019 ◽  
Vol 20 (11) ◽  
pp. 2756 ◽  
Author(s):  
Amanda C. Daulagala ◽  
Mary Catherine Bridges ◽  
Antonis Kourtidis
Keyword(s):  
Cell Behavior ◽  
Colonic Epithelium ◽  
Core Component ◽  
Critical Function ◽  
The Core ◽  
Colon Tumorigenesis ◽  
Barrier Formation ◽  
Traditional Roles ◽  
E Cadherin

E-cadherin is the core component of epithelial adherens junctions, essential for tissue development, differentiation, and maintenance. It is also fundamental for tissue barrier formation, a critical function of epithelial tissues. The colon or large intestine is lined by an epithelial monolayer that encompasses an E-cadherin-dependent barrier, critical for the homeostasis of the organ. Compromised barriers of the colonic epithelium lead to inflammation, fibrosis, and are commonly observed in colorectal cancer. In addition to its architectural role, E-cadherin is also considered a tumor suppressor in the colon, primarily a result of its opposing function to Wnt signaling, the predominant driver of colon tumorigenesis. Beyond these well-established traditional roles, several studies have portrayed an evolving role of E-cadherin as a signaling epicenter that regulates cell behavior in response to intra- and extra-cellular cues. Intriguingly, these recent findings also reveal tumor-promoting functions of E-cadherin in colon tumorigenesis and new interacting partners, opening future avenues of investigation. In this Review, we focus on these emerging aspects of E-cadherin signaling, and we discuss their implications in colon biology and disease.

scholarly journals Substrate-gated docking of pore subunit Tha4 in the TatC cavity initiates Tat translocase assembly

2014 ◽  
Vol 205 (1) ◽  
pp. 51-65 ◽  
Author(s):  
Cassie Aldridge ◽  
Xianyue Ma ◽  
Fabien Gerard ◽  
Kenneth Cline
Keyword(s):  
Signal Peptide ◽  
Receptor Complex ◽  
Core Component ◽  
The Core ◽  
Contact Sites ◽  
Contact Data ◽  
Folded Proteins ◽  
Twin Arginine Translocase ◽  
Enclosed Chamber

The twin-arginine translocase (Tat) transports folded proteins across tightly sealed membranes. cpTatC is the core component of the thylakoid translocase and coordinates transport through interactions with the substrate signal peptide and other Tat components, notably the Tha4 pore-forming component. Here, Cys–Cys matching mapped Tha4 contact sites on cpTatC and assessed the role of signal peptide binding on Tha4 assembly with the cpTatC–Hcf106 receptor complex. Tha4 made contact with a peripheral cpTatC site in nonstimulated membranes. In the translocase, Tha4 made an additional contact within the cup-shaped cavity of cpTatC that likely seeds Tha4 polymerization to form the pore. Substrate binding triggers assembly of Tha4 onto the interior site. We provide evidence that the substrate signal peptide inserts between cpTatC subunits arranged in a manner that conceivably forms an enclosed chamber. The location of the inserted signal peptide and the Tha4–cpTatC contact data suggest a model for signal peptide–gated Tha4 entry into the chamber to form the translocase.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

410: Cleavage of E-Cadherin and the Role of an 80KDa Fragment in the Metastatic Progression of Prostate Cancer

2004 ◽  
Vol 171 (4S) ◽  
pp. 108-108
Author(s):  
Rainer Kuefer ◽  
Kathleen Day ◽  
Jonathan Rios-Doria ◽  
Matthias Hofer ◽  
Arul Chinnaiyan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Progression ◽  
E Cadherin

Does a Ribosome Really Read? On the Cognitive Roots and Heuristic Value of Linguistic Metaphors in Molecular Genetics. Part 2

2020 ◽  
Vol 63 (2) ◽  
pp. 46-62
Author(s):  
Suren T. Zolyan
Keyword(s):  
Information Processing ◽  
Genetic Information ◽  
Formal Organization ◽  
Dual Nature ◽  
Reading Frame ◽  
The Core ◽  
Genetic Information Processing ◽  
Cognitive Frame ◽  
Effective Instrument

We discuss the role of linguistic metaphors as a cognitive frame for the understanding of genetic information processing. The essential similarity between language and genetic information processing has been recognized since the very beginning, and many prominent scholars have noted the possibility of considering genes and genomes as texts or languages. Most of the core terms in molecular biology are based on linguistic metaphors. The processing of genetic information is understood as some operations on text – writing, reading and editing and their specification (encoding/decoding, proofreading, transcription, translation, reading frame). The concept of gene reading can be traced from the archaic idea of the equation of Life and Nature with the Book. Thus, the genetics itself can be metaphorically represented as some operations on text (deciphering, understanding, code-breaking, transcribing, editing, etc.), which are performed by scientists. At the same time linguistic metaphors portrayed gene entities also as having the ability of reading. In the case of such “bio-reading” some essential features similar to the processes of human reading can be revealed: this is an ability to identify the biochemical sequences based on their function in an abstract system and distinguish between type and its contextual tokens of the same type. Metaphors seem to be an effective instrument for representation, as they make possible a two-dimensional description: biochemical by its experimental empirical results and textual based on the cognitive models of comprehension. In addition to their heuristic value, linguistic metaphors are based on the essential characteristics of genetic information derived from its dual nature: biochemical by its substance, textual (or quasi-textual) by its formal organization. It can be concluded that linguistic metaphors denoting biochemical objects and processes seem to be a method of description and explanation of these heterogeneous properties.

Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology

2020 ◽  
Vol 23 ◽  
Author(s):  
Xiao Zhou ◽  
Xiao-Fei Zhang ◽  
Dong-Yan Guo ◽  
Yan-Jun Yang ◽  
Lin Liu ◽  
...  
Keyword(s):  
Febrile Seizures ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Compounds ◽  
Potential Core ◽  
R Language ◽  
The Core ◽  
Multiple Factors ◽  
Therapeutic Mechanism

Objective: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription which can be effective in treating febrile seizures (FS) and has few researches on the mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. Materials and Methods: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS was obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software to locked the potential core compounds and targets of FS. The R language and ClusterProfiler software package were adopt to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets were revealed. Results: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened which involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS regulated FS in the pathogenesis and therapeutic mechanism of FS was discussed and clarified. Conclusions: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS was preliminarily revealed through the analysis of network pharmacology data, which is consistent with the principle of multi-compounds compatibility of TCM prescriptions and unified treatment of diseases from multiple angles, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

Acid ceramidase, a double-edged sword in cancer aggression: A minireview

2020 ◽  
Vol 20 ◽  
Author(s):  
Helen Shiphrah Vethakanraj ◽  
Niveditha Chandrasekaran ◽  
Ashok Kumar Sekar
Keyword(s):  
Cell Fate ◽  
Cancer Progression ◽  
Potential Role ◽  
Tumour Progression ◽  
Acid Ceramidase ◽  
The Core ◽  
The Past ◽  
Sphingosine 1 Phosphate ◽  
Key Enzyme

: Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.

The Fox Diet

2018 ◽  
Author(s):  
Yochai Benkler ◽  
Robert Faris ◽  
Hal Roberts
Keyword(s):  
First Year ◽  
Right Wing ◽  
Justice Department ◽  
Fox News ◽  
The Core ◽  
Deep State ◽  
Media Ecosystem ◽  
Conservative Media ◽  
The Right

This chapter focuses on the role of the dominant player in conservative media, Fox News, during the first year of Donald Trump’s presidency. It looks at three case studies to illustrate how Fox News used its position at the core of the right-wing media ecosystem repeatedly to mount propaganda attacks in support of Trump: the Michael Flynn firing in March 2017, when Fox adopted the “deep state” framing of the entire controversy; the James Comey firing and Robert Mueller appointment in May 2017; when Fox propagated the Seth Rich murder conspiracy; and in October and November, when the arrests of Paul Manafort and guilty plea of Flynn seemed to mark a new level of threat to the president, Fox reframed the Uranium One story as an attack on the integrity of the FBI and Justice Department officials in charge of the investigation.

scholarly journals The role of AGN activity in the building up of the BCG at z ∼ 1.6

2019 ◽  
Vol 15 (S356) ◽  
pp. 280-284
Author(s):  
Angela Bongiorno ◽  
Andrea Travascio
Keyword(s):  
Galaxy Cluster ◽  
Cluster Galaxy ◽  
X Ray ◽  
Groups Of Galaxies ◽  
Star Forming ◽  
The Core ◽  
The Galaxy ◽  
Multi Wavelength

AbstractXDCPJ0044.0-2033 is one of the most massive galaxy cluster at z ∼1.6, for which a wealth of multi-wavelength photometric and spectroscopic data have been collected during the last years. I have reported on the properties of the galaxy members in the very central region (∼ 70kpc × 70kpc) of the cluster, derived through deep HST photometry, SINFONI and KMOS IFU spectroscopy, together with Chandra X-ray, ALMA and JVLA radio data.In the core of the cluster, we have identified two groups of galaxies (Complex A and Complex B), seven of them confirmed to be cluster members, with signatures of ongoing merging. These galaxies show perturbed morphologies and, three of them show signs of AGN activity. In particular, two of them, located at the center of each complex, have been found to host luminous, obscured and highly accreting AGN (λ = 0.4−0.6) exhibiting broad Hα line. Moreover, a third optically obscured type-2 AGN, has been discovered through BPT diagram in Complex A. The AGN at the center of Complex B is detected in X-ray while the other two, and their companions, are spatially related to radio emission. The three AGN provide one of the closest AGN triple at z > 1 revealed so far with a minimum (maximum) projected distance of 10 kpc (40 kpc). The discovery of multiple AGN activity in a highly star-forming region associated to the crowded core of a galaxy cluster at z ∼ 1.6, suggests that these processes have a key role in shaping the nascent Brightest Cluster Galaxy, observed at the center of local clusters. According to our data, all galaxies in the core of XDCPJ0044.0-2033 could form a BCG of M* ∼ 1012Mȯ hosting a BH of 2 × 108−109Mȯ, in a time scale of the order of 2.5 Gyrs.

scholarly journals Avolition as the core negative symptom in schizophrenia: relevance to pharmacological treatment development

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Gregory P. Strauss ◽  
Lisa A. Bartolomeo ◽  
Philip D. Harvey
Keyword(s):  
Negative Symptom ◽  
Negative Symptoms ◽  
Clinical Trial Design ◽  
Core Component ◽  
Treatment Target ◽  
Global Improvement ◽  
Treatment Development ◽  
The Core ◽  
Current Review ◽  
Symptom Domains

AbstractNegative symptoms have long been considered a core component of schizophrenia. Modern conceptualizations of the structure of negative symptoms posit that there are at least two broad dimensions (motivation and pleasure and diminished expression) or perhaps five separable domains (avolition, anhedonia, asociality, blunted affect, alogia). The current review synthesizes a body of emerging research indicating that avolition may have a special place among these dimensions, as it is generally associated with poorer outcomes and may have distinct neurobiological mechanisms. Network analytic findings also indicate that avolition is highly central and interconnected with the other negative symptom domains in schizophrenia, and successfully remediating avolition results in global improvement in the entire constellation of negative symptoms. Avolition may therefore reflect the most critical treatment target within the negative symptom construct. Implications for targeted treatment development and clinical trial design are discussed.

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