Revealing novel interactions between oak and Tubakia species: evidence of the efficacy of the sentinel arboreta strategy

2021 ◽  
Author(s):  
Carmen Morales-Rodríguez ◽  
Giorgia Bastianelli ◽  
MariaPia Aleandri ◽  
H. Tuğba Doğmuş-Lehtijärvi ◽  
Funda Oskay ◽  
...  
Keyword(s):  
Novel Interactions

scholarly journals Novel Interactions of ESCRT-III with LIP5 and VPS4 and their Implications for ESCRT-III Disassembly

2008 ◽  
Vol 19 (6) ◽  
pp. 2661-2672 ◽  
Author(s):  
Soomin Shim ◽  
Samuel A. Merrill ◽  
Phyllis I. Hanson
Keyword(s):  
Atpase Activity ◽  
Binding Site ◽  
Binding Sites ◽  
Essential Role ◽  
Multivesicular Body ◽  
The Other ◽  
Aaa Atpase ◽  
Direct Binding ◽  
Novel Interactions

The AAA+ ATPase VPS4 plays an essential role in multivesicular body biogenesis and is thought to act by disassembling ESCRT-III complexes. VPS4 oligomerization and ATPase activity are promoted by binding to LIP5. LIP5 also binds to the ESCRT-III like protein CHMP5/hVps60, but how this affects its function remains unclear. Here we confirm that LIP5 binds tightly to CHMP5, but also find that it binds well to additional ESCRT-III proteins including CHMP1B, CHMP2A/hVps2–1, and CHMP3/hVps24 but not CHMP4A/hSnf7–1 or CHMP6/hVps20. LIP5 binds to a different region within CHMP5 than within the other ESCRT-III proteins. In CHMP1B and CHMP2A, its binding site encompasses sequences at the proteins' extreme C-termini that overlap with “MIT interacting motifs” (MIMs) known to bind to VPS4. We find unexpected evidence of a second conserved binding site for VPS4 in CHMP2A and CHMP1B, suggesting that LIP5 and VPS4 may bind simultaneously to these proteins despite the overlap in their primary binding sites. Finally, LIP5 binds preferentially to soluble CHMP5 but instead to polymerized CHMP2A, suggesting that the newly defined interactions between LIP5 and ESCRT-III proteins may be regulated by ESCRT-III conformation. These studies point to a role for direct binding between LIP5 and ESCRT-III proteins that is likely to complement LIP5's previously described ability to regulate VPS4 activity.

Mobility-as-a-Service: Simulation of Multi-Modal Operations in Low-Density Cities

2021 ◽  
pp. 036119812110398
Author(s):  
Mohamed El-Agroudy ◽  
Hatem Abou-Senna ◽  
Essam Radwan
Keyword(s):  
Performance Measures ◽  
Magic Bullet ◽  
Low Density ◽  
The Novel ◽  
Review Of The Literature ◽  
Modal Interactions ◽  
New Approach ◽  
Novel Interactions ◽  
Alternative Scenarios ◽  
Urban Characteristics

In the case of the low-density city, empirical evidence continuously demonstrates that transit investment is not a magic bullet. Desirable outcomes are not guaranteed and are often dependent on development density and other urban characteristics. Mobility-as-a-service (MaaS) presents a new approach: a digital platform providing access to multi-modal travel alternatives and totally comprehensive integrated trip-making, planning, and payment services. Review of the literature highlights shortcomings in traditional transportation planning by examining aspects of multi-modal planning such as adoption, parterships, operations, integration, capacity implications, and impact analyses. To enhance the practice of multi-modal planning, the following experiment evaluates various performance measures and inter-modal interactions on International Drive in Orlando, Florida, U.S., via D- and I-optimal experimental designs in a simulated MaaS network. Alternative scenarios are developed comparing varied modal shares across five travel modes: personal vehicles, transit, ridesourcing (or ride-hailing), micro-mobility, and walking. The modal effects are analyzed to highlight the strengths and weakness of each mode under a variety of congestion conditions. While transit enjoys the lowest impact per person, ridesourcing demonstrates adverse effects across all measures. Based on the novel interactions of transit and ridesourcing with directional demand, strategies are outlined for optimizing ridesourcing-transit integration to reduce route travel time, queuing, and overall network delay. The performance impacts of curbside facilities are also discussed for improved multi-modal integration at the street level. These findings are applied to propose a framework for effective planning and implementation of mobility services in low-density cities, focused on operations, city-level connectivity, and curbside management.

Crystallographic Structures of Human α-Thrombin Complexed to Peptide Boronic Acids Lacking a Positive Charge at P1. Evidence of Novel Interactions

1997 ◽  
Vol 119 (41) ◽  
pp. 9935-9936 ◽  
Author(s):  
Emmanuel Skordalakes ◽  
Richard Tyrell ◽  
Said Elgendy ◽  
Christopher A. Goodwin ◽  
Donovan Green ◽  
...  
Keyword(s):  
Positive Charge ◽  
Boronic Acids ◽  
Crystallographic Structures ◽  
Novel Interactions

scholarly journals Copper Alters Aggregation Behavior of Prion Protein and Induces Novel Interactions between Its N- and C-terminal Regions

2011 ◽  
Vol 286 (44) ◽  
pp. 38533-38545 ◽  
Author(s):  
Abhay Kumar Thakur ◽  
Atul Kumar Srivastava ◽  
Volety Srinivas ◽  
Kandala Venkata Ramana Chary ◽  
Chintalagiri Mohan Rao
Keyword(s):  
Prion Protein ◽  
Aggregation Behavior ◽  
Novel Interactions

scholarly journals Double-edge sword roles of iron in driving energy production versus instigating ferroptosis

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Shuping Zhang ◽  
Wei Xin ◽  
Gregory J. Anderson ◽  
Ruibin Li ◽  
Ling Gao ◽  
...  
Keyword(s):  
Fenton Reaction ◽  
Energy Production ◽  
Iron Homeostasis ◽  
Regulated Cell Death ◽  
Double Edge ◽  
Double Edge Sword ◽  
Novel Interactions ◽  
Metabolic Activities ◽  
Species Production

AbstractIron is vital for many physiological functions, including energy production, and dysregulated iron homeostasis underlies a number of pathologies. Ferroptosis is a recently recognized form of regulated cell death that is characterized by iron dependency and lipid peroxidation, and this process has been reported to be involved in multiple diseases. The mechanisms underlying ferroptosis are complex, and involve both well-described pathways (including the iron-induced Fenton reaction, impaired antioxidant capacity, and mitochondrial dysfunction) and novel interactions linked to cellular energy production. In this review, we examine the contribution of iron to diverse metabolic activities and their relationship to ferroptosis. There is an emphasis on the role of iron in driving energy production and its link to ferroptosis under both physiological and pathological conditions. In conclusion, excess reactive oxygen species production driven by disordered iron metabolism, which induces Fenton reaction and/or impairs mitochondrial function and energy metabolism, is a key inducer of ferroptosis.

scholarly journals PRIMA: a gene-centered, RNA-to-protein method for mapping RNA-protein interactions

2016 ◽  
Author(s):  
Alex M. Tamburino ◽  
Ebru Kaymak ◽  
Shaleen Shrestha ◽  
Amy D. Holdorf ◽  
Sean P. Ryder ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Small Rna ◽  
Rna Binding ◽  
Mrna Translation ◽  
Single Experiment ◽  
Novel Interactions ◽  
Transcriptional Gene Regulation ◽  
Rna Interaction ◽  
Eukaryotic Genomes

SUMMARYInteractions between RNA binding protein (RBP) and mRNAs are critical to post-transcriptional gene regulation. Eukaryotic genomes encode thousands of mRNAs and hundreds of RBPs. However, in contrast to interactions between transcription factors (TFs) and DNA, the interactome between RBPs and RNA has been explored for only a small number of proteins and RNAs. This is largely because the focus has been on using ‘protein-centered’ (RBP-to-RNA) interaction mapping methods that identify the RNAs with which an individual RBP interacts. While powerful, these methods cannot as of yet be applied to the entire RBPome. Moreover, it may be desirable for a researcher to identify the repertoire of RBPs that can interact with an mRNA of interest – in a ‘gene-centered’ manner, yet few such techniques are available. Here, we present Protein-RNA Interaction Mapping Assay (PRIMA) with which an RNA ‘bait’ can be tested versus multiple RBP ‘preys’ in a single experiment. PRIMA is a translation-based assay that examines interactions in the yeast cytoplasm, the cellular location of mRNA translation. We show that PRIMA can be used with small RNA elements, as well as with full-length Caenorhabditis elegans 3′UTRs. PRIMA faithfully recapitulates numerous well-characterized RNA-RBP interactions and also identified novel interactions, some of which were confirmed in vivo. We envision that PRIMA will provide a complementary tool to expand the depth and scale with which the RNA-RBP interactome can be explored.

scholarly journals Perturbation-based gene regulatory network inference to unravel oncogenic mechanisms

2019 ◽  
Author(s):  
Daniel Morgan ◽  
Matthew Studham ◽  
Andreas Tjärnberg ◽  
Holger Weishaupt ◽  
Fredrik J. Swartling ◽  
...  
Keyword(s):  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Network Inference ◽  
Gene Regulatory Network Inference ◽  
Validation Data ◽  
Regulatory Interactions ◽  
Link Type ◽  
Gene Regulatory ◽  
Novel Interactions

AbstractThe gene regulatory network (GRN) of human cells encodes mechanisms to ensure proper functioning. However, if this GRN is dysregulated, the cell may enter into a disease state such as cancer. Understanding the GRN as a system can therefore help identify novel mechanisms underlying disease, which can lead to new therapies. Reliable inference of GRNs is however still a major challenge in systems biology.To deduce regulatory interactions relevant to cancer, we applied a recent computational inference framework to data from perturbation experiments in squamous carcinoma cell line A431. GRNs were inferred using several methods, and the false discovery rate was controlled by the NestBoot framework. We developed a novel approach to assess the predictiveness of inferred GRNs against validation data, despite the lack of a gold standard. The best GRN was significantly more predictive than the null model, both in crossvalidated benchmarks and for an independent dataset of the same genes under a different perturbation design. It agrees with many known links, in addition to predicting a large number of novel interactions from which a subset was experimentally validated. The inferred GRN captures regulatory interactions central to cancer-relevant processes and thus provides mechanistic insights that are useful for future cancer research.Data available at GSE125958Inferred GRNs and inference statistics available at https://dcolin.shinyapps.io/CancerGRN/ Software available at https://bitbucket.org/sonnhammergrni/genespider/src/BFECV/Author SummaryCancer is the second most common cause of death globally, and although cancer treatments have improved in recent years, we need to understand how regulatory mechanisms are altered in cancer to combat the disease efficiently. By applying gene perturbations and inference of gene regulatory networks to 40 genes known or suspected to have a role in cancer due to interactions with the oncogene MYC, we deduce their underlying regulatory interactions. Using a recent computational framework for inference together with a novel method for cross validation, we infer a reliable regulatory model of this system in a completely data driven manner, not reliant on literature or priors. The novel interactions add to the understanding of the progressive oncogenic regulatory process and may provide new targets for therapy.

The roles of hedgehog, wingless and lines in patterning the dorsal epidermis in Drosophila

Development ◽  
1996 ◽  
Vol 122 (4) ◽  
pp. 1083-1092 ◽  
Author(s):  
P. Bokor ◽  
S. DiNardo
Keyword(s):  
Cell Types ◽  
Imaginal Discs ◽  
Drosophila Embryo ◽  
Cell Type ◽  
Signaling Center ◽  
Novel Interactions ◽  
Dorsal Epidermis ◽  
Segment Pattern

Rows of cells that flank the parasegment boundary make up a signaling center within the epidermis of the Drosophila embryo. Signals emanating from these cells, encoded by hedgehog (hh) and wingless (wg), are shown to be required for all segment pattern dorsally. Wg activity is required for the differentiation of one cell type, constituting half the parasegment. The gene lines appears to act in parallel to the Wg pathway in the elaboration of this cell type. Hh activity is responsible for three other cell types in the parasegment. Some cell types are specified as Hh activity and interfere with the function of patched, analogous to patterning of imaginal discs. However, some pattern is independent of the antagonism of patched by Hh, and relies instead on novel interactions with lines. Lastly, we provide evidence that decapentaplegic does not mediate patterning by Hh in the dorsal epidermis.

Crowdfunding, Financing Constraints, and Real Effects

2020 ◽  
Vol 66 (8) ◽  
pp. 3561-3580 ◽  
Author(s):  
Praveen Kumar ◽  
Nisan Langberg ◽  
David Zvilichovsky
Keyword(s):  
Demand Uncertainty ◽  
Spot Price ◽  
Financing Constraints ◽  
Optimal Contract ◽  
External Financing ◽  
Real Effects ◽  
Discriminating Power ◽  
Individual Demand ◽  
Novel Interactions ◽  
The Cost

We study the feasibility and optimal design of presale crowdfunding contracts where participating consumers pay a premium above the future expected spot price and financially constrained entrepreneurs balance the potential product–market distortions introduced through presale crowdfunding against the cost of traditional external financing. Our analysis shows how such crowdfunding contracts enable the execution of projects that could not be otherwise undertaken and highlights novel interactions between the cost of capital, demand uncertainty, and production. Tighter financing constraints reduce the ability of the monopolist to extract surplus but, contrary to the usual result, may increase production. We evaluate how uncertainty and market size reduce the price-discriminating power of the monopolist and affect the optimal contract regime. Nevertheless, we show how such presale price-discriminating contracts are implementable even when the number of potential consumers is relatively high and their individual demand is stochastic. This paper was accepted by Gustavo Manso, finance.

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