scholarly journals Oncometabolite induced primary cilia loss in pheochromocytoma

2019 ◽  
Vol 26 (1) ◽  
pp. 165-180 ◽  
Author(s):  
Samuel M O’Toole ◽  
David S Watson ◽  
Tatiana V Novoselova ◽  
Lisa E L Romano ◽  
Peter J King ◽  
...  
Keyword(s):  
Therapeutic Intervention ◽  
General Feature ◽  
Primary Cilia ◽  
Germline Mutations ◽  
Structure And Function ◽  
Endocrine Tumors ◽  
Pheochromocytoma Cell ◽  
Transcriptional Changes ◽  
Key Drivers ◽  
And Function

Primary cilia are sensory organelles involved in regulation of cellular signaling. Cilia loss is frequently observed in tumors; yet, the responsible mechanisms and consequences for tumorigenesis remain unclear. We demonstrate that cilia structure and function is disrupted in human pheochromocytomas – endocrine tumors of the adrenal medulla. This is concomitant with transcriptional changes within cilia-mediated signaling pathways that are associated with tumorigenesis generally and pheochromocytomas specifically. Importantly, cilia loss was most dramatic in patients with germline mutations in the pseudohypoxia-linked genes SDHx and VHL. Using a pheochromocytoma cell line derived from rat, we show that hypoxia and oncometabolite-induced pseudohypoxia are key drivers of cilia loss and identify that this is dependent on activation of an Aurora-A/HDAC6 cilia resorption pathway. We also show cilia loss drives dramatic transcriptional changes associated with proliferation and tumorigenesis. Our data provide evidence for primary cilia dysfunction contributing to pathogenesis of pheochromocytoma by a hypoxic/pseudohypoxic mechanism and implicates oncometabolites as ciliary regulators. This is important as pheochromocytomas can cause mortality by mechanisms including catecholamine production and malignant transformation, while hypoxia is a general feature of solid tumors. Moreover, pseudohypoxia-induced cilia resorption can be pharmacologically inhibited, suggesting potential for therapeutic intervention.

Ecosystems processes

2018 ◽  
Author(s):  
Karen J. Esler ◽  
Anna L. Jacobsen ◽  
R. Brandon Pratt
Keyword(s):  
Ecosystem Function ◽  
Mineral Nutrients ◽  
Structure And Function ◽  
Water Dynamics ◽  
Ecosystem Level ◽  
Key Drivers ◽  
And Function ◽  
Mediterranean Type Ecosystems

Ecosystems are assemblages of organisms interacting with one another and their environment (Chapter 1). Key to the functioning of ecosystems is the flow of energy, carbon, mineral nutrients, and water in these systems. The numerous processes involved are chiefly driven by climate, soil, and fire (Chapter 2). In cases where the key drivers are the same in different areas, then ecosystems should converge in their structure and function, which has been a motivation for comparing across mediterranean-type climate (MTC) regions. Convergence of MTC regions has been evaluated, but such comparisons at the ecosystem level are challenging because ecosystems are complex and dynamic entities. Here we review carbon, nutrient, and water dynamics of mediterranean-type ecosystems in the context of ecosystem function. As nutrients in soils are low in some MTC regions, we review how this has led to unique adaptations to meet this challenge.

scholarly journals Structure and function of polycystin channels in primary cilia

2020 ◽  
Vol 72 ◽  
pp. 109626
Author(s):  
Chau My Ta ◽  
Thuy N. Vien ◽  
Leo C.T. Ng ◽  
Paul G. DeCaen
Keyword(s):  
Primary Cilia ◽  
Structure And Function ◽  
And Function

scholarly journals The Kinocilia of Cochlear Hair Cells: Structures, Functions, and Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Difei Wang ◽  
Jun Zhou
Keyword(s):  
Auditory System ◽  
Hair Cells ◽  
Primary Cilia ◽  
Structure And Function ◽  
Biochemical Reactions ◽  
Cochlear Hair Cells ◽  
Evolutionarily Conserved ◽  
Genes Encoding ◽  
And Function ◽  
The Brain

Primary cilia are evolutionarily conserved and highly specialized organelles that protrude from cell membranes. Mutations in genes encoding ciliary proteins can cause structural and functional ciliary defects and consequently multiple diseases, collectively termed ciliopathies. The mammalian auditory system is responsible for perceiving external sound stimuli that are ultimately processed in the brain through a series of physical and biochemical reactions. Here we review the structure and function of the specialized primary cilia of hair cells, termed kinocilia, found in the mammalian auditory system. We also discuss areas that might prove amenable for therapeutic management of auditory ciliopathies.

scholarly journals Changes in chondrocyte primary cilia structure and function are associated with altered mechanoregulation in Alkaptonuria

2016 ◽  
Vol 24 ◽  
pp. S174-S175
Author(s):  
S.D. Thorpe ◽  
S. Gambassi ◽  
R. Patel ◽  
A. Santucci ◽  
M.M. Knight
Keyword(s):  
Primary Cilia ◽  
Structure And Function ◽  
And Function

Primary cilia: a link between hormone signalling and endocrine-related cancers?

2016 ◽  
Vol 44 (5) ◽  
pp. 1227-1234 ◽  
Author(s):  
Samuel M. O'Toole ◽  
J. Paul Chapple
Keyword(s):  
Primary Cilia ◽  
Structure And Function ◽  
Growing Body ◽  
And Function ◽  
Hormone Signalling

Primary cilia are sensory organelles that play a role as signalling hubs. Disruption of primary cilia structure and function is increasingly recognised in a range of cancers, with a growing body of evidence suggesting that ciliary disruption contributes to tumourigenesis. This review considers the role of primary cilia in the pathogenesis of endocrine-related cancers.

scholarly journals The Sorghum bicolor Root Exudate Sorgoleone Shapes Bacterial Communities and Delays Network Formation

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Peng Wang ◽  
Yen Ning Chai ◽  
Rebecca Roston ◽  
Franck E. Dayan ◽  
Daniel P. Schachtman
Keyword(s):  
Secondary Metabolites ◽  
Microbial Communities ◽  
Root Exudates ◽  
Soil Microbes ◽  
Structure And Function ◽  
Soil Microbe ◽  
Primary And Secondary Metabolites ◽  
Microbe Interactions ◽  
Key Drivers ◽  
And Function

ABSTRACT Primary and secondary metabolites exuded from roots are key drivers of root-soil microbe interactions that contribute to the structure and function of microbial communities. Studies with model plants have begun to reveal the complex interactions between root exudates and soil microbes, but little is known about the influence of specialized exudates from crop plants. The aims of this work were to understand whether sorgoleone, a unique lipophilic secondary benzoquinone exuded only from the root hairs of sorghum, influences belowground microbial community structure in the field, to assess the effect of purified sorgoleone on the cultured bacteria from field soils, and to determine whether sorgoleone inhibits nitrification under field conditions. Studies were conducted comparing wild-type sorghum and lines with genetically reduced sorgoleone exudation. In the soil near roots and rhizosphere, sorgoleone influenced microbial community structure as measured by β-diversity and network analysis. Under greenhouse conditions, the soil nitrogen content was an important factor in determining the impacts of sorgoleone. Sorgoleone delayed the formation of the bacterial and archaeal networks early in plant development and only inhibited nitrification at specific sampling times under field conditions. Sorgoleone was also shown to both inhibit and promote cultured bacterial isolate growth in laboratory tests. These findings provide new insights into the role of secondary metabolites in shaping the composition and function of the sorghum root-associated bacterial microbiomes. Understanding how root exudates modify soil microbiomes may potentially unlock an important tool for enhancing crop sustainability and yield in our changing environment. IMPORTANCE Plant roots exude a complex mixture of metabolites into the rhizosphere. Primary and secondary metabolites exuded from roots are key drivers of root-soil microbe interactions that contribute to the structure and function of microbial communities in agricultural and natural ecosystems. Previous work on plant root exudates and their influence on soil microbes has mainly been restricted to model plant species. Plant are a diverse group of organisms and produce a wide array of different secondary metabolites. Therefore, it is important to go beyond studies of model plants to fully understand the diverse repertoire of root exudates in crop plant species that feed human populations. Extending studies to a wider array of root exudates will provide a more comprehensive understanding of how the roots of important food crops interact with highly diverse soil microbial communities. This will provide information that could lead to tailoring root exudates for the development of more beneficial plant-soil microbe interactions that will benefit agroecosystem productivity.

Structure and function of neural networks in the retina

1988 ◽  
Vol 46 ◽  
pp. 26-27
Author(s):  
Peter Sterling
Keyword(s):  
Ganglion Cells ◽  
Three Dimensional ◽  
Structure And Function ◽  
Synaptic Connections ◽  
Visual Axis ◽  
One Dimensional ◽  
Cat Retina ◽  
Ultrathin Sections ◽  
And Function ◽  
Insight Into

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.

Osseointegration interface of calcified bone and endosseous implants

1992 ◽  
Vol 50 (2) ◽  
pp. 1096-1097
Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley
Keyword(s):  
Structure And Function ◽  
Titanium Implants ◽  
En Bloc ◽  
Endosseous Implants ◽  
Ultrastructural Studies ◽  
The Past ◽  
Cacodylate Buffer ◽  
One Year ◽  
And Function

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.

Use of human autoantibodies and immunoelectron microscopy to study structure and function of the nucleolus and nuclear bodies

1992 ◽  
Vol 50 (1) ◽  
pp. 506-507
Author(s):  
Robert L. Ochs
Keyword(s):  
Electron Microscopy ◽  
Structure And Function ◽  
Nuclear Bodies ◽  
Nuclear Interior ◽  
Coiled Bodies ◽  
Interchromatin Granules ◽  
And Function ◽  
Conventional Electron Microscopy ◽  
Perichromatin Granules ◽  
Perichromatin Fibrils

By conventional electron microscopy, the formed elements of the nuclear interior include the nucleolus, chromatin, interchromatin granules, perichromatin granules, perichromatin fibrils, and various types of nuclear bodies (Figs. 1a-c). Of these structures, all have been reasonably well characterized structurally and functionally except for nuclear bodies. The most common types of nuclear bodies are simple nuclear bodies and coiled bodies (Figs. 1a,c). Since nuclear bodies are small in size (0.2-1.0 μm in diameter) and infrequent in number, they are often overlooked or simply not observed in any random thin section. The rat liver hepatocyte in Fig. 1b is a case in point. Historically, nuclear bodies are more prominent in hyperactive cells, they often occur in proximity to nucleoli (Fig. 1c), and sometimes they are observed to “bud off” from the nucleolar surface.

Sign in / Sign up

Export Citation Format

Share Document