CRISPR-based editing reveals edge-specific effects in biological networks

AbstractUnraveling the properties of biological networks is central to understanding normal and disease cellular phenotypes. Networks consist of functional elements (nodes) that form a variety of diverse connections (edges) with each node being a hub for multiple edges. Herein, in contrast to node-centric network perturbation and analysis approaches, we present a high-throughput CRISPR-based methodology for delineating the role of network edges. Ablation of network edges using a library targeting 93 miRNA target sites in 71 genes reveals numerous edges that control, with variable importance, cellular survival under stress. To compare the impact of removing nodes versus edges in a biological network, we dissect a specific p53-microRNA pathway. In summary, we demonstrate that network edges are critical to the function and stability of biological networks. Our results introduce a novel genetic screening opportunity via edge ablation and highlight a new dimension in biological network analysis.

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PetriScape - A plugin for discrete Petri net simulations in Cytoscape

Journal of Integrative Bioinformatics ◽

10.1515/jib-2016-284 ◽

2016 ◽

Vol 13 (1) ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Diogo Almeida ◽

Vasco Azevedo ◽

Artur Silva ◽

Jan Baumbach

Keyword(s):

Petri Nets ◽

Petri Net ◽

Biological Networks ◽

Computational Analysis ◽

Biological Network ◽

Global Network ◽

Data Sets ◽

Biological Network Analysis ◽

Network Properties ◽

Sbml Format

SummarySystems biology plays a central role for biological network analysis in the post-genomic era. Cytoscape is the standard bioinformatics tool offering the community an extensible platform for computational analysis of the emerging cellular network together with experimental omics data sets. However, only few apps/plugins/tools are available for simulating network dynamics in Cytoscape 3. Many approaches of varying complexity exist but none of them have been integrated into Cytoscape as app/plugin yet. Here, we introduce PetriScape, the first Petri net simulator for Cytoscape. Although discrete Petri nets are quite simplistic models, they are capable of modeling global network properties and simulating their behaviour. In addition, they are easily understood and well visualizable. PetriScape comes with the following main functionalities: (1) import of biological networks in SBML format, (2) conversion into a Petri net, (3) visualization as Petri net, and (4) simulation and visualization of the token flow in Cytoscape. PetriScape is the first Cytoscape plugin for Petri nets. It allows a straightforward Petri net model creation, simulation and visualization with Cytoscape, providing clues about the activity of key components in biological networks.

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Measuring the Impact of Welfare Benefits on Welfare Durations: State Stratified Partial Likelihood and Fixed Effect Approaches

Topics in Economic Analysis & Policy ◽

10.2202/1538-0653.1121 ◽

2004 ◽

Vol 4 (1) ◽

Author(s):

John M Fitzgerald

Keyword(s):

Fixed Effects ◽

Partial Likelihood ◽

Welfare Programs ◽

Cross Sectional ◽

Welfare Benefits ◽

Specific Effects ◽

High Benefit ◽

The Impact ◽

The U.S

Abstract Previous studies of welfare durations in the U.S. have analyzed the role of welfare benefits on the length of time recipients remain on welfare. Typically these studies use individual data and estimate the benefit effects based on both cross-sectional variation across locations and time variation within locations. Cross sectional results on benefit effects may be biased due to unobserved state specific differences in welfare programs or attitudes. This paper compares two strategies for dealing with the problem when estimating welfare exit hazard models: stratification of baseline hazards by state and the inclusion of state fixed effects in the hazards. Although the results show that high benefit states appear to have unobserved characteristics that lead to longer spells, the results also show that increases in welfare benefits do not directly increase welfare durations once one controls for state specific effects.

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Distinct functions of AKT isoforms in breast cancer: a comprehensive review

Cell Communication and Signaling ◽

10.1186/s12964-019-0450-3 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 22

Author(s):

Nico Hinz ◽

Manfred Jücker

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Tumor Growth ◽

Therapy Response ◽

Akt Signaling ◽

Migration And Invasion ◽

Akt Isoforms ◽

Specific Effects ◽

The Impact

Abstract Background AKT, also known as protein kinase B, is a key element of the PI3K/AKT signaling pathway. Moreover, AKT regulates the hallmarks of cancer, e.g. tumor growth, survival and invasiveness of tumor cells. After AKT was discovered in the early 1990s, further studies revealed that there are three different AKT isoforms, namely AKT1, AKT2 and AKT3. Despite their high similarity of 80%, the distinct AKT isoforms exert non-redundant, partly even opposing effects under physiological and pathological conditions. Breast cancer as the most common cancer entity in women, frequently shows alterations of the PI3K/AKT signaling. Main content A plethora of studies addressed the impact of AKT isoforms on tumor growth, metastasis and angiogenesis of breast cancer as well as on therapy response and overall survival in patients. Therefore, this review aimed to give a comprehensive overview about the isoform-specific effects of AKT in breast cancer and to summarize known downstream and upstream mechanisms. Taking account of conflicting findings among the studies, the majority of the studies reported a tumor initiating role of AKT1, whereas AKT2 is mainly responsible for tumor progression and metastasis. In detail, AKT1 increases cell proliferation through cell cycle proteins like p21, p27 and cyclin D1 and impairs apoptosis e.g. via p53. On the downside AKT1 decreases migration of breast cancer cells, for instance by regulating TSC2, palladin and EMT-proteins. However, AKT2 promotes migration and invasion most notably through regulation of β-integrins, EMT-proteins and F-actin. Whilst AKT3 is associated with a negative ER-status, findings about the role of AKT3 in regulation of the key properties of breast cancer are sparse. Accordingly, AKT1 is mutated and AKT2 is amplified in some cases of breast cancer and AKT isoforms are associated with overall survival and therapy response in an isoform-specific manner. Conclusions Although there are several discussed hypotheses how isoform specificity is achieved, the mechanisms behind the isoform-specific effects remain mostly unrevealed. As a consequence, further effort is necessary to achieve deeper insights into an isoform-specific AKT signaling in breast cancer and the mechanism behind it.

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Biological network analysis and comparison: mining new biological knowledge

Open Computer Science ◽

10.2478/s13537-011-0013-1 ◽

2011 ◽

Vol 1 (2) ◽

Cited By ~ 1

Author(s):

Valeria Fionda

Keyword(s):

Life Cycle ◽

Network Analysis ◽

Biological Networks ◽

Biological Network ◽

Biological Knowledge ◽

Biological Network Analysis ◽

Cell Life ◽

The World ◽

Automated Tools

AbstractThe mechanisms underlying life machinery are still not completely understood. Something is known, something is “probably” known, other things are still unknown. Scientists all over the world are working very hard to clarify the processes regulating the cell life cycle and bioinformaticians try to support them by developing specialized automated tools. Within the plethora of applications devoted to the study of life mechanisms, tools for the analysis and comparison of biological networks are catching the attention of many researchers. It is interesting to investigate why.

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The Impact of H2S on Obesity-Associated Metabolic Disturbances

Antioxidants ◽

10.3390/antiox10050633 ◽

2021 ◽

Vol 10 (5) ◽

pp. 633

Author(s):

Ferran Comas ◽

José María Moreno-Navarrete

Keyword(s):

Immune Functions ◽

Post Translational Modification ◽

Metabolic Disturbances ◽

Alcoholic Fatty Liver ◽

Cellular Survival ◽

Current State ◽

Human Disorders ◽

The Impact ◽

New Evidence

Over the last several decades, hydrogen sulfide (H2S) has gained attention as a new signaling molecule, with extensive physiological and pathophysiological roles in human disorders affecting vascular biology, immune functions, cellular survival, metabolism, longevity, development, and stress resistance. Apart from its known functions in oxidative stress and inflammation, new evidence has emerged revealing that H2S carries out physiological functions by targeting proteins, enzymes, and transcription factors through a post-translational modification known as persulfidation. This review article provides a critical overview of the current state of the literature addressing the role of H2S in obesity-associated metabolic disturbances, with particular emphasis on its mechanisms of action in obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases.

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Myeloid cells as therapeutic targets in neuroinflammation after stroke: Specific roles of neutrophils and neutrophil–platelet interactions

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x18795789 ◽

2018 ◽

Vol 38 (12) ◽

pp. 2150-2164 ◽

Cited By ~ 35

Author(s):

Alicia García-Culebras ◽

Violeta Durán-Laforet ◽

Carolina Peña-Martínez ◽

Iván Ballesteros ◽

Jesús M Pradillo ◽

...

Keyword(s):

Cell Lineage ◽

Myeloid Cell ◽

Stroke Outcome ◽

Local Inflammatory Response ◽

Injured Brain ◽

Ischemic Tissue ◽

Key Characteristics ◽

Cellular Phenotypes ◽

The Impact

Ischemic brain injury causes a local inflammatory response, involving the activation of resident brain cells such as microglia and the recruitment of infiltrating immune cells. Increasing evidence supports that plasticity of the myeloid cell lineage is determinant for the specific role of these cells on stroke outcome, from initiation and maintenance to resolution of post-ischemic inflammation. The aim of this review is to summarize some of the key characteristics of these cells and the mechanisms for their recruitment into the injured brain through interactions with platelets, endothelial cells and other leukocytes. Also, we discuss the existence of different leukocyte subsets in the ischemic tissue and, specifically, the impact of different myeloid phenotypes on stroke outcome, with special emphasis on neutrophils and their interplay with platelets. Knowledge of these cellular phenotypes and interactions may pave the way to new therapies able to promote protective immune responses and tissue repair after cerebral ischemia.

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The Impact of Visual Stereotypes on Judgments about Rape

Swiss Journal of Psychology ◽

10.1024/1421-0185/a000178 ◽

2016 ◽

Vol 75 (3) ◽

pp. 133-140

Author(s):

Robert Busching ◽

Johannes Lutz

Keyword(s):

Mental Representations ◽

Irrelevant Information ◽

Clear Distinction ◽

Rape Myth ◽

Facial Features ◽

Reverse Correlation ◽

Correlation Technique ◽

Specific Effects ◽

Legal Judgments ◽

The Impact

Abstract. Legally irrelevant information like facial features is used to form judgments about rape cases. Using a reverse-correlation technique, it is possible to visualize criminal stereotypes and test whether these representations influence judgments. In the first step, images of the stereotypical faces of a rapist, a thief, and a lifesaver were generated. These images showed a clear distinction between the lifesaver and the two criminal representations, but the criminal representations were rather similar. In the next step, the images were presented together with rape scenarios, and participants (N = 153) indicated the defendant’s level of liability. Participants with high rape myth acceptance scores attributed a lower level of liability to a defendant who resembled a stereotypical lifesaver. However, no specific effects of the image of the stereotypical rapist compared to the stereotypical thief were found. We discuss the findings with respect to the influence of visual stereotypes on legal judgments and the nature of these mental representations.

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Intergroup Threat and Outgroup Attitudes

Social Psychology ◽

10.1027/1864-9335/a000127 ◽

2013 ◽

Vol 44 (5) ◽

pp. 311-319 ◽

Cited By ~ 12

Author(s):

Marco Brambilla ◽

David A. Butz

Keyword(s):

Gay Men ◽

Social Group ◽

Welfare Recipients ◽

Intergroup Attitudes ◽

Social Policies ◽

Intergroup Threat ◽

Economic Threat ◽

The Impact ◽

General Climate

Two studies examined the impact of macrolevel symbolic threat on intergroup attitudes. In Study 1 (N = 71), participants exposed to a macrosymbolic threat (vs. nonsymbolic threat and neutral topic) reported less support toward social policies concerning gay men, an outgroup whose stereotypes implies a threat to values, but not toward welfare recipients, a social group whose stereotypes do not imply a threat to values. Study 2 (N = 78) showed that, whereas macrolevel symbolic threat led to less favorable attitudes toward gay men, macroeconomic threat led to less favorable attitudes toward Asians, an outgroup whose stereotypes imply an economic threat. These findings are discussed in terms of their implications for understanding the role of a general climate of threat in shaping intergroup attitudes.

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