scholarly journals Getting the whole picture: High content screening using three-dimensional cellular model systems and whole animal assays

2016 ◽  
Vol 91 (2) ◽  
pp. 152-159 ◽  
Author(s):  
Janos Kriston-Vizi ◽  
Horst Flotow
Keyword(s):  
Three Dimensional ◽  
Model Systems ◽  
High Content Screening ◽  
Cellular Model

Casimir forces and vacuum energy

2017 ◽  
Author(s):  
Serge Reynaud ◽  
Astrid Lambrecht
Keyword(s):  
Casimir Force ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Thermal Fluctuations ◽  
Model Systems ◽  
Vacuum Field ◽  
Force Measurements ◽  
Casimir Forces ◽  
Current State ◽  
Field Fluctuations

The Casimir force is an effect of quantum vacuum field fluctuations, with applications in many domains of physics. The ideal expression obtained by Casimir, valid for perfect plane mirrors at zero temperature, has to be modified to take into account the effects of the optical properties of mirrors, thermal fluctuations, and geometry. After a general introduction to the Casimir force and a description of the current state of the art for Casimir force measurements and their comparison with theory, this chapter presents pedagogical treatments of the main features of the theory of Casimir forces for one-dimensional model systems and for mirrors in three-dimensional space.

Controlling charge transfer in fullerene/phthalocyanine electron donor-acceptor conjugates/hybrids

2009 ◽  
Vol 13 (10) ◽  
pp. 1034-1039 ◽  
Author(s):  
Wolfgang Seitz ◽  
Axel Kahnt ◽  
Dirk M. Guldi ◽  
Tomas Torres
Keyword(s):  
Three Dimensional ◽  
Reorganization Energy ◽  
Model Systems ◽  
Transfer Reactions ◽  
Dimensional Electron ◽  
Specific Composition ◽  
Donor And Acceptor ◽  
Donor Acceptor ◽  
Light Harvesting Antenna ◽  
Energetic Charge

Fullerenes and phthalocyanines are ideally suited for devising integrated, multi-component model systems to transmit and process solar energy. Implementation of C 60 as a three-dimensional electron acceptor bears great promises on account of its small reorganization energy in electron transfer reactions and has exerted a noteworthy impact on the improvement of light-induced charge separation. This mini-review describes how the specific composition of phthalocyanines chromophores associated with C 60 – yielding artificial light-harvesting antenna and reaction center mimics – have been elegantly utilized to tune the electronic couplings between donor and acceptor sites. Specifically, the effects that these parameters have on the rate, yield and lifetime of the energetic charge-separated states are considered.

scholarly journals CAL-1 as Cellular Model System to Study CCR7-Guided Human Dendritic Cell Migration

2021 ◽  
Vol 12 ◽  
Author(s):  
Edith Uetz-von Allmen ◽  
Guerric P. B. Samson ◽  
Vladimir Purvanov ◽  
Takahiro Maeda ◽  
Daniel F. Legler
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Neoplastic Cell ◽  
Model System ◽  
Model Systems ◽  
Cellular Model ◽  
Gm Csf ◽  
Endogenous Expression ◽  
Dendritic Cell Migration ◽  
Spatio Temporal

Dendritic cells (DCs) are potent and versatile professional antigen-presenting cells and central for the induction of adaptive immunity. The ability to migrate and transport peripherally acquired antigens to draining lymph nodes for subsequent cognate T cell priming is a key feature of DCs. Consequently, DC-based immunotherapies are used to elicit tumor-antigen specific T cell responses in cancer patients. Understanding chemokine-guided DC migration is critical to explore DCs as cellular vaccines for immunotherapeutic approaches. Currently, research is hampered by the lack of appropriate human cellular model systems to effectively study spatio-temporal signaling and CCR7-driven migration of human DCs. Here, we report that the previously established human neoplastic cell line CAL-1 expresses the human DC surface antigens CD11c and HLA-DR together with co-stimulatory molecules. Importantly, if exposed for three days to GM-CSF, CAL-1 cells induce the endogenous expression of the chemokine receptor CCR7 upon encountering the clinically approved TLR7/8 agonist Resiquimod R848 and readily migrate along chemokine gradients. Further, we demonstrate that CAL-1 cells can be genetically modified to express fluorescent (GFP)-tagged reporter proteins to study and visualize signaling or can be gene-edited using CRISPR/Cas9. Hence, we herein present the human CAL-1 cell line as versatile and valuable cellular model system to effectively study human DC migration and signaling.

scholarly journals Organoid Models for Cancer Research

2019 ◽  
Vol 3 (1) ◽  
pp. 223-234 ◽  
Author(s):  
Hans Clevers ◽  
David A. Tuveson
Keyword(s):  
Cancer Research ◽  
Tumor Microenvironment ◽  
Personalized Medicine ◽  
High Throughput ◽  
Stromal Cells ◽  
Transcriptome Sequencing ◽  
Cancer Biology ◽  
Three Dimensional ◽  
Model Systems ◽  
Liver Cancers

Organoid cultures have emerged as powerful model systems accelerating discoveries in cellular and cancer biology. These three-dimensional cultures are amenable to diverse techniques, including high-throughput genome and transcriptome sequencing, as well as genetic and biochemical perturbation, making these models well suited to answer a variety of questions. Recently, organoids have been generated from diverse human cancers, including breast, colon, pancreas, prostate, bladder, and liver cancers, and studies involving these models are expanding our knowledge of the etiology and characteristics of these malignancies. Co-cultures of cancer organoids with non-neoplastic stromal cells enable investigation of the tumor microenvironment. In addition, recent studies have established that organoids have a place in personalized medicine approaches. Here, we describe the application of organoid technology to cancer discovery and treatment.

scholarly journals In vitro model systems to study androgen receptor signaling in prostate cancer

2013 ◽  
Vol 20 (2) ◽  
pp. R49-R64 ◽  
Author(s):  
Natalie Sampson ◽  
Hannes Neuwirt ◽  
Martin Puhr ◽  
Helmut Klocker ◽  
Iris E Eder
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cellular Response ◽  
Three Dimensional ◽  
Model Systems ◽  
Transfer Of Knowledge ◽  
Prostate Epithelial Cells ◽  
Technological Advances ◽  
Culture Models

Prostate cancer (PCa) is one of the most common causes of male cancer-related death in Western nations. The cellular response to androgens is mediated via the androgen receptor (AR), a ligand-inducible transcription factor whose dysregulation plays a key role during PCa development and progression following androgen deprivation therapy, the current mainstay systemic treatment for advanced PCa. Thus, a better understanding of AR signaling and new strategies to abrogate AR activity are essential for improved therapeutic intervention. Consequently, a large number of experimental cell culture models have been established to facilitate in vitro investigations into the role of AR signaling in PCa development and progression. These different model systems mimic distinct stages of this heterogeneous disease and exhibit differences with respect to AR expression/status and androgen responsiveness. Technological advances have facilitated the development of in vitro systems that more closely reflect the physiological setting, for example via the use of three-dimensional coculture to study the interaction of prostate epithelial cells with the stroma, endothelium, immune system and tissue matrix environment. This review provides an overview of the most commonly used in vitro cell models currently available to study AR signaling with particular focus on their use in addressing key questions relating to the development and progression of PCa. It is hoped that the continued development of in vitro models will provide more biologically relevant platforms for mechanistic studies, drug discovery and design ensuring a more rapid transfer of knowledge from the laboratory to the clinic.

scholarly journals Preclinical Modelling of PDA: Is Organoid the New Black?

2019 ◽  
Vol 20 (11) ◽  
pp. 2766 ◽  
Author(s):  
Sabrina D’Agosto ◽  
Silvia Andreani ◽  
Aldo Scarpa ◽  
Vincenzo Corbo
Keyword(s):  
Therapeutic Intervention ◽  
Culture System ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Three Dimensional ◽  
Model Systems ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools ◽  
Precision Oncology ◽  
Individual Patient Level

Pancreatic ductal adenocarcinoma (PDA) is a malignancy of the exocrine pancreas with the worst prognosis among all solid tumours, and soon to become the second leading cause of cancer-related deaths. A more comprehensive understanding of the molecular mechanisms underlying this disease is crucial to the development of diagnostic tools as well as to the identification of more effective therapies. High-frequency mutations in PDA occur in “undruggable” genes, and molecular subtyping based on bulk transcriptome analysis does not yet nominate valid therapeutic intervention strategies. Genome-wide sequencing studies have also demonstrated a considerable intra- and inter-patient’s genetic heterogeneity, which further complicate this dire scenario. More than in other malignancies, functionalization of the PDA genome and preclinical modelling at the individual patient level appear necessary to substantially improve survival rates for pancreatic cancer patients. Traditional human PDA models, including monolayer cell cultures and patient-derived xenografts, have certainly led to valuable biological insights in the past years. However, those model systems suffer from several limitations that have contributed to the lack of concordance between preclinical and clinical studies for PDA. Pancreatic ductal organoids have recently emerged as a reliable culture system to establish models from both normal and neoplastic pancreatic tissues. Pancreatic organoid cultures can be efficiently generated from small tissue biopsies, which opens up the possibility of longitudinal studies in individual patients. A proof-of-concept study has demonstrated that patient-derived PDA organoids are able to predict responses to conventional chemotherapy. The use of this three-dimensional culture system has already improved our understanding of PDA biology and promises to implement precision oncology by enabling the alignment of preclinical and clinical platforms to guide therapeutic intervention in PDA.

scholarly journals UPF1 silenced cellular model systems for screening of read-through agents active on β039 thalassemia point mutation

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Francesca Salvatori ◽  
Mariangela Pappadà ◽  
Giulia Breveglieri ◽  
Elisabetta D’Aversa ◽  
Alessia Finotti ◽  
...  
Keyword(s):  
Point Mutation ◽  
Model Systems ◽  
Cellular Model

The thylakoid membranes of cyanobacteria: structure, dynamics and function

1999 ◽  
Vol 26 (7) ◽  
pp. 671 ◽  
Author(s):  
Conrad W. Mullineaux
Keyword(s):  
Genetic Manipulation ◽  
Three Dimensional ◽  
Thylakoid Membranes ◽  
Model Systems ◽  
Photosynthetic Membrane ◽  
Membrane Function ◽  
Intact Membrane ◽  
Photosynthetic Organism ◽  
Dynamics And Function ◽  
And Function

In recent years there has been remarkable progress in determining the three-dimensional structures of photosynthetic complexes. A new challenge is emerging: can we understand the organisation and interaction of those complexes in the intact photosynthetic membrane? Intact membranes are complex, dynamic systems. If we are to understand the function of the intact membrane, we will need to understand the organisation of the complexes, how they can diffuse and interact in the membrane, how they are assembled, repaired and broken down, and how their function is regulated. Cyanobacteria have some crucial advantages as model systems. The complete sequencing of the Synechocystis 6803 genome, coupled with the ease of genetic manipulation of Synechocystis (and certain other cyanobacteria) have given us a unique tool for studying a photosynthetic organism. Furthermore, some cyanobacteria have a very simple, regular thylakoid membrane structure. The unique geometry of photosynthetic membranes of these cyanobacteria will greatly facilitate biophysical studies of membrane function. This review summarises recent progress in understanding the structure, function and dynamics of cyanobacterial thylakoid membranes, highlights the questions that remain to be answered and suggests some possible approaches towards solving those questions.

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