scholarly journals Topography of corticopontine projections is controlled by postmitotic expression of the area-mapping gene Nr2f1

2021 ◽  
Author(s):  
Chiara Tocco ◽  
Martin Ovsthus ◽  
Jan G Bjaalie ◽  
Trygve Brauns Leergaard ◽  
Michele Studer
Keyword(s):  
Three Dimensional ◽  
Model Systems ◽  
Brain Atlas ◽  
Voluntary Movements ◽  
Pontine Nuclei ◽  
Axonal Projections ◽  
Molecular Determinants ◽  
Mapping Gene ◽  
Postmitotic Neurons ◽  
Layer V

Axonal projections from layer V neurons of distinct neocortical areas are topographically organized into discrete clusters within the pontine nuclei during the establishment of voluntary movements. However, the molecular determinants controlling corticopontine connectivity are insufficiently understood. Here, we show that an intrinsic cortical genetic program driven by Nr2f1 graded expression in cortical progenitors and postmitotic neurons is directly implicated in the organization of corticopontine topographic mapping. Transgenic mice lacking cortical expression of Nr2f1 and exhibiting areal organization defects were used as model systems to investigate the arrangement of corticopontine projections. Combining three-dimensional digital brain atlas tools, Cre-dependent mouse lines, and axonal tracing, we show that Nr2f1 expression in postmitotic neurons spatially and temporally controls somatosensory topographic projections, whereas expression in progenitor cells influences the ratio between corticopontine and corticospinal fibers passing the pontine nuclei. We conclude that cortical gradients of area patterning genes are directly implicated in the establishment of a topographic somatotopic mapping from the cortex onto pontine nuclei.

Detection and mapping of interactions between chromatin and the nuclear envelope in drosophila embryos

1995 ◽  
Vol 53 ◽  
pp. 764-765
Author(s):  
W.F. Marshall ◽  
A.F. Dernburg ◽  
B. Harmon ◽  
J.W. Sedat
Keyword(s):  
Nuclear Envelope ◽  
Chromatin Condensation ◽  
Three Dimensional ◽  
Physiological Role ◽  
Nuclear Surface ◽  
Intact Cells ◽  
Molecular Determinants ◽  
Surface Harmonic ◽  
Drosophila Embryos

Interactions between chromatin and nuclear envelope (NE) have been implicated in chromatin condensation, gene regulation, nuclear reassembly, and organization of chromosomes within the nucleus. To further investigate the physiological role played by such interactions, it will be necessary to determine which loci specifically interact with the nuclear envelope. This will not only facilitate identification of the molecular determinants of this interaction, but will also allow manipulation of the pattern of chromatin-NE interactions to probe possible functions. We have developed a microscopic approach to detect and map chromatin-NE interactions inside intact cells.Fluorescence in situ hybridization (FISH) is used to localize specific chromosomal regions within the nucleus of Drosophila embryos and anti-lamin immunofluorescence is used to detect the nuclear envelope. Widefield deconvolution microscopy is then used to obtain a three-dimensional image of the sample (Fig. 1). The nuclear surface is represented by a surface-harmonic expansion (Fig 2). A statistical test for association of the FISH spot with the surface is then performed.

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 Spindle-Shaped Neurons in the Human Posteromedial (Precuneus) Cortex

2022 ◽  
Vol 13 ◽  
Author(s):  
Francisco Javier Fuentealba-Villarroel ◽  
Josué Renner ◽  
Arlete Hilbig ◽  
Oliver J. Bruton ◽  
Alberto A. Rasia-Filho
Keyword(s):  
Brain Area ◽  
Three Dimensional ◽  
Golgi Method ◽  
Cortical Layer ◽  
Von Economo Neurons ◽  
Dendritic Length ◽  
Adult Humans ◽  
Layer V ◽  
Layer Vi

The human posteromedial cortex (PMC), which includes the precuneus (PC), represents a multimodal brain area implicated in emotion, conscious awareness, spatial cognition, and social behavior. Here, we describe the presence of Nissl-stained elongated spindle-shaped neurons (suggestive of von Economo neurons, VENs) in the cortical layer V of the anterior and central PC of adult humans. The adapted “single-section” Golgi method for postmortem tissue was used to study these neurons close to pyramidal ones in layer V until merging with layer VI polymorphic cells. From three-dimensional (3D) reconstructed images, we describe the cell body, two main longitudinally oriented ascending and descending dendrites as well as the occurrence of spines from proximal to distal segments. The primary dendritic shafts give rise to thin collateral branches with a radial orientation, and pleomorphic spines were observed with a sparse to moderate density along the dendritic length. Other spindle-shaped cells were observed with straight dendritic shafts and rare branches or with an axon emerging from the soma. We discuss the morphology of these cells and those considered VENs in cortical areas forming integrated brain networks for higher-order activities. The presence of spindle-shaped neurons and the current discussion on the morphology of putative VENs address the need for an in-depth neurochemical and transcriptomic characterization of the PC cytoarchitecture. These findings would include these spindle-shaped cells in the synaptic and information processing by the default mode network and for general intelligence in healthy individuals and in neuropsychiatric disorders involving the PC in the context of the PMC functioning.

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.

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