scholarly journals First ComprehensiveIn SilicoAnalysis of the Functional and Structural Consequences of SNPs in HumanGalNAc-T1Gene

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Hussein Sheikh Ali Mohamoud ◽  
Muhammad Ramzan Manwar Hussain ◽  
Ashraf A. El-Harouni ◽  
Noor Ahmad Shaik ◽  
Zaheer Ulhaq Qasmi ◽  
...  
Keyword(s):  
Disease Susceptibility ◽  
Cell Signalling ◽  
Gene Mutations ◽  
Cell Types ◽  
Biological Tissues ◽  
Coding Regions ◽  
Wide Range ◽  
Glycosylation Pathway ◽  
And Function ◽  
Regulatory Snps

GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-typeO-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association ofGalNAc-T1gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs ofGalNAc-T1gene in order to identify and characterize them. Our concordantin silicoanalysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs ofGalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified inGalNAc-T1by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function ofGalNAc-T1enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases.

scholarly journals Mapping calcium dynamics in a developing tubular structure

2020 ◽  
Author(s):  
Jorgen Hoyer ◽  
Morsal Saba ◽  
Daniel Dondorp ◽  
Kushal Kolar ◽  
Riccardo Esposito ◽  
...  
Keyword(s):  
Cell Types ◽  
Feedback Mechanism ◽  
Adult Brain ◽  
Actin Dynamics ◽  
Cytoskeletal Network ◽  
Notochord Cell ◽  
Wide Range ◽  
Store Operated Calcium Entry ◽  
And Function ◽  
Cell Intercalation

AbstractCalcium is a ubiquitous and versatile second messenger that plays a central role in the development and function of a wide range of cell types, tissues and organs. Despite significant recent progress in the understanding of calcium (Ca2+) signalling in organs such as the developing and adult brain, we have relatively little knowledge of the contribution of Ca2+ to the development of tubes, structures widely present in multicellular organisms. Here we image Ca2+ dynamics in the developing notochord of Ciona intestinalis. We show that notochord cells exhibit distinct Ca2+ dynamics during specific morphogenetic events such as cell intercalation, cell elongation and tubulogenesis. We used an optogenetically controlled Ca2+ actuator to show that sequestration of Ca2+ results in defective notochord cell intercalation, and pharmacological inhibition to reveal that stretch-activated ion channels (SACs), inositol triphosphate receptor (IP3R) signalling, Store Operated Calcium Entry (SOCE), Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and gap junctions are required for regulating notochord Ca2+ activity during tubulogenesis. Cytoskeletal rearrangements drive the cell shape changes that accompany tubulogenesis. In line with this, we show that Ca2+ signalling modulates reorganization of the cytoskeletal network across the morphogenetic events leading up to and during tubulogenesis of the notochord. We additionally demonstrate that perturbation of the actin cytoskeleton drastically remodels Ca2+ dynamics, suggesting a feedback mechanism between actin dynamics and Ca2+ signalling during notochord development. This work provides a framework to quantitatively define how Ca2+ signalling regulates tubulogenesis using the notochord as model organ, a defining structure of all chordates.

scholarly journals Identification and characterization of differentially active pools of type IIα phosphatidylinositol 4-kinase activity in unstimulated A431 cells

2003 ◽  
Vol 376 (2) ◽  
pp. 497-503 ◽  
Author(s):  
Mark G. WAUGH ◽  
Shane MINOGUE ◽  
Deena BLUMENKRANTZ ◽  
J. Simon ANDERSON ◽  
J. Justin HSUAN
Keyword(s):  
Kinase Activity ◽  
Cell Signalling ◽  
Cell Types ◽  
Intrinsic Activity ◽  
A431 Cells ◽  
Cell Functions ◽  
Subcellular Membrane ◽  
Phosphatidylinositol Kinase ◽  
Wide Range ◽  
Phosphatidylinositol 4

The seven known polyphosphoinositides have been implicated in a wide range of regulated and constitutive cell functions, including cell-surface signalling, vesicle trafficking and cytoskeletal reorganization. In order to understand the spatial and temporal control of these diverse cell functions it is necessary to characterize the subcellular distribution of a wide variety of polyphosphoinositide synthesis and signalling events. The predominant phosphatidylinositol kinase activity in many mammalian cell types involves the synthesis of the signalling precursor, phosphatidylinositol 4-phosphate, in a reaction catalysed by the recently cloned PI4KIIα (type IIα phosphatidylinositol 4-kinase). However the regulation of this enzyme and the cellular distribution of its product in different organelles are very poorly understood. This report identifies the existence, in unstimulated cells, of two major subcellular membrane fractions, which contain PI4KIIα possessing different levels of intrinsic activity. Separation of these membranes from each other and from contaminating activities was achieved by density gradient ultracentrifugation at pH 11 in a specific detergent mixture in which both membrane fractions, but not other membranes, were insoluble. Kinetic comparison of the purified membrane fractions revealed a 4-fold difference in Km for phosphatidylinositol and a 3.5-fold difference in Vmax, thereby indicating a different mechanism of regulation to that described previously for agonist-stimulated cells. These marked differences in basal activity and the occurrence of this isozyme in multiple organelles emphasize the need to investigate cell signalling via PI4KIIα at the level of individual organelles rather than whole-cell lysates.

scholarly journals The Roles of Primary Cilia in Cardiovascular Diseases

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 233 ◽  
Author(s):  
Rajasekharreddy Pala ◽  
Maha Jamal ◽  
Qamar Alshammari ◽  
Surya Nauli
Keyword(s):  
Cardiovascular Diseases ◽  
Primary Cilia ◽  
Cell Types ◽  
Molecular Defects ◽  
Flow Sensing ◽  
Intracellular Signals ◽  
Wide Range ◽  
No Signaling ◽  
Vascular Endothelia ◽  
And Function

Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, termed ciliopathies, with phenotypes ranging from polycystic kidney disease, liver disorders, mental retardation, and obesity to cardiovascular diseases. Primary cilia in vascular endothelia protrude into the lumen of blood vessels and function as molecular switches for calcium (Ca2+) and nitric oxide (NO) signaling. As mechanosensory organelles, endothelial cilia are involved in blood flow sensing. Dysfunction in endothelial cilia contributes to aberrant fluid-sensing and thus results in vascular disorders, including hypertension, aneurysm, and atherosclerosis. This review focuses on the most recent findings on the roles of endothelial primary cilia within vascular biology and alludes to the possibility of primary cilium as a therapeutic target for cardiovascular disorders.

scholarly journals Structure and function of the immune system in the spleen

2019 ◽  
Vol 4 (33) ◽  
pp. eaau6085 ◽  
Author(s):  
Steven M. Lewis ◽  
Adam Williams ◽  
Stephanie C. Eisenbarth
Keyword(s):  
Cell Types ◽  
Structure And Function ◽  
Lymphoid Organ ◽  
The Body ◽  
Human Spleen ◽  
Cell Clearance ◽  
Wide Range ◽  
Abnormal Cells ◽  
Cell Organization ◽  
And Function

The spleen is the largest secondary lymphoid organ in the body and, as such, hosts a wide range of immunologic functions alongside its roles in hematopoiesis and red blood cell clearance. The physical organization of the spleen allows it to filter blood of pathogens and abnormal cells and facilitate low-probability interactions between antigen-presenting cells (APCs) and cognate lymphocytes. APCs specific to the spleen regulate the T and B cell response to these antigenic targets in the blood. This review will focus on cell types, cell organization, and immunologic functions specific to the spleen and how these affect initiation of adaptive immunity to systemic blood-borne antigens. Potential differences in structure and function between mouse and human spleen will also be discussed.

scholarly journals Bone Anabolic Effects of Soluble Si:In VitroStudies with Human Mesenchymal Stem Cells and CD14+ Osteoclast Precursors

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
J. Costa-Rodrigues ◽  
S. Reis ◽  
A. Castro ◽  
M. H. Fernandes
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Plasma Levels ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Osteoclast Precursors ◽  
Wide Range ◽  
Basal Plasma ◽  
Important Player ◽  
And Function

Silicon (Si) is indispensable for many cellular processes including bone tissue metabolism. In this work, the effects of Si on human osteogenesis and osteoclastogenesis were characterized. Human mesenchymal stem cells (hMSC) and CD14+ stem cells, as osteoblast and osteoclast precursors, were treated with a wide range of Si concentrations, covering the physiological plasma levels. Si promoted a dose-dependent increase in hMSC proliferation, differentiation, and function, at levels similar to the normal basal plasma levels. Additionally, a decrease in the expression of the osteoclastogenic activators M-CSF and RANKL was observed. Also, Si elicited a decrease in osteoclastogenesis, which became significant at higher concentrations, as those observed after meals. Among the intracellular mechanisms studied, an upregulation of MEK and PKC signalling pathways was observed in both cell types. In conclusion, Si appears to have a direct positive effect on human osteogenesis, at basal plasma levels. On the other hand, it also seemed to be an inhibitor of osteoclastogenesis, but at higher concentrations, though yet in the physiological range. Further, an indirect effect of Si on osteoclastogenesis may also occur, through a downregulation of M-CSF and RANKL expression by osteoblasts. Thus, Si may be an important player in bone anabolic regenerative approaches.

scholarly journals Morphology and function of three VIP-expressing amacrine cell types in the mouse retina

2015 ◽  
Vol 114 (4) ◽  
pp. 2431-2438 ◽  
Author(s):  
Alejandro Akrouh ◽  
Daniel Kerschensteiner
Keyword(s):  
Mammalian Species ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Light Responses ◽  
Wide Range ◽  
Asymmetric Distributions ◽  
And Function

Amacrine cells (ACs) are the most diverse class of neurons in the retina. The variety of signals provided by ACs allows the retina to encode a wide range of visual features. Of the 30–50 AC types in mammalian species, few have been studied in detail. Here, we combine genetic and viral strategies to identify and to characterize morphologically three vasoactive intestinal polypeptide-expressing GABAergic AC types (VIP1-, VIP2-, and VIP3-ACs) in mice. Somata of VIP1- and VIP2-ACs reside in the inner nuclear layer and somata of VIP3-ACs in the ganglion cell layer, and they show asymmetric distributions along the dorsoventral axis of the retina. Neurite arbors of VIP-ACs differ in size (VIP1-ACs ≈ VIP3-ACs > VIP2-ACs) and stratify in distinct sublaminae of the inner plexiform layer. To analyze light responses and underlying synaptic inputs, we target VIP-ACs under 2-photon guidance for patch-clamp recordings. VIP1-ACs depolarize strongly to light increments (ON) over a wide range of stimulus sizes but show size-selective responses to light decrements (OFF), depolarizing to small and hyperpolarizing to large stimuli. The switch in polarity of OFF responses is caused by pre- and postsynaptic surround inhibition. VIP2- and VIP3-ACs both show small depolarizations to ON stimuli and large hyperpolarizations to OFF stimuli but differ in their spatial response profiles. Depolarizations are caused by ON excitation outweighing ON inhibition, whereas hyperpolarizations result from pre- and postsynaptic OFF-ON crossover inhibition. VIP1-, VIP2-, and VIP3-ACs thus differ in response polarity and spatial tuning and contribute to the diversity of inhibitory and neuromodulatory signals in the retina.

scholarly journals Outlook for Wound Healing Technologies (a Review)

2020 ◽  
Vol 10 (2) ◽  
pp. 130-136
Author(s):  
V. V. Chebotarev ◽  
Z. R. Khismatullina ◽  
L. K. Nasyrova
Keyword(s):  
Tissue Engineering ◽  
Wound Healing ◽  
Medical Science ◽  
Living Organism ◽  
Biological Tissues ◽  
Structural Level ◽  
Skin Substitutes ◽  
Wide Range ◽  
Artificial Extracellular Matrix ◽  
And Function

Tissue engineering is a medical science dealing with reproduction of biological tissues and organs. This area of medicine opens avenues for creation of organs and tissues using biomaterials and nanostructures to sustain their development, maintenance and function repair in a living organism. The scope of tissue engineering is an artificial recreation of tissues at the fi nest structural level. Prerequisite requirements are a cell source (a donor), artificial extracellular matrix and growth factor. The first organ, which was extracorporally created and successfully introduced in medical practice, is skin. Recent years have witnessed a major leap in 3D technology for reproduction of biological structures. Increasing attention is being paid towards controlled design and production of 2D–3D structures consisting of biological materials and viable cells, the procedure defined as bioproduction or bioprototyping. Skin substitutes obtained with the bioprototyping technology possess a wide range of medical applications, primarily to compensate for resident skin deficiency in wound healing.

scholarly journals Flagellar Synchronization Is a Simple Alternative to Cell Cycle Synchronization for Ciliary and Flagellar Studies

mSphere ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Soumita Dutta ◽  
Prachee Avasthi
Keyword(s):  
Cell Cycle ◽  
Chlamydomonas Reinhardtii ◽  
Cell Types ◽  
Model System ◽  
Content Type ◽  
Cell Synchronization ◽  
Cilium Formation ◽  
Wide Range ◽  
Cilia And Flagella ◽  
And Function

ABSTRACT Cilia and flagella are highly conserved antenna-like organelles that found in nearly all mammalian cell types. They perform sensory and motile functions contributing to numerous physiological and developmental processes. Defects in their assembly and function are implicated in a wide range of human diseases ranging from retinal degeneration to cancer. Chlamydomonas reinhardtii is an algal model system for studying mammalian cilium formation and function. Here, we report a simple synchronization method that allows detection of small changes in ciliary length by minimizing variability in the population. We find that this method alters the key relationship between cell size and the amount of protein accumulated for flagellar growth. This provides a rapid alternative to traditional methods of cell synchronization for uncovering novel regulators of cilia. The unicellular green alga Chlamydomonas reinhardtii is an ideal model organism for studies of ciliary function and assembly. In assays for biological and biochemical effects of various factors on flagellar structure and function, synchronous culture is advantageous for minimizing variability. Here, we have characterized a method in which 100% synchronization is achieved with respect to flagellar length but not with respect to the cell cycle. The method requires inducing flagellar regeneration by amputation of the entire cell population and limiting regeneration time. This results in a maximally homogeneous distribution of flagellar lengths at 3 h postamputation. We found that time-limiting new protein synthesis during flagellar synchronization limits variability in the unassembled pool of limiting flagellar protein and variability in flagellar length without affecting the range of cell volumes. We also found that long- and short-flagella mutants that regenerate normally require longer and shorter synchronization times, respectively. By minimizing flagellar length variability using a simple method requiring only hours and no changes in media, flagellar synchronization facilitates the detection of small changes in flagellar length resulting from both chemical and genetic perturbations in Chlamydomonas. This method increases our ability to probe the basic biology of ciliary size regulation and related disease etiologies. IMPORTANCE Cilia and flagella are highly conserved antenna-like organelles that found in nearly all mammalian cell types. They perform sensory and motile functions contributing to numerous physiological and developmental processes. Defects in their assembly and function are implicated in a wide range of human diseases ranging from retinal degeneration to cancer. Chlamydomonas reinhardtii is an algal model system for studying mammalian cilium formation and function. Here, we report a simple synchronization method that allows detection of small changes in ciliary length by minimizing variability in the population. We find that this method alters the key relationship between cell size and the amount of protein accumulated for flagellar growth. This provides a rapid alternative to traditional methods of cell synchronization for uncovering novel regulators of cilia.

scholarly journals Signaling roles of phosphoinositides in the retina

2020 ◽  
pp. jlr.TR120000806 ◽  
Author(s):  
Raju V. S. Rajala
Keyword(s):  
Cell Types ◽  
Cellular Functions ◽  
Parent Molecule ◽  
Phosphoinositide Signaling ◽  
Wide Range ◽  
The Many ◽  
And Function ◽  
Different Cell Types

The field of phosphoinositide signaling has expanded significantly in recent years. Phosphoinositides (PIs) are universal signaling molecules that directly interact with membrane proteins or with cytosolic proteins containing domains that directly bind phosphoinositides and are recruited to cell membranes. Through the activities of PI kinases and PI phosphatases, seven distinct phosphoinositide lipid molecules are formed from the parent molecule phosphatidylinositol. PI signals regulate a wide range of cellular functions, including cytoskeletal assembly, membrane binding and fusion, ciliogenesis, vesicular transport, and signal transduction. Given the many excellent reviews on phosphoinositide kinases, phosphoinositide phosphatases, and PIs in general, in this review, we discuss recent studies and advances in PI lipid signaling in the retina. We specifically focus on PI lipids from vertebrate (e.g. bovine, rat, mice, toad, and zebrafish) and invertebrate (e.g. drosophila, horseshoe crab, and squid) retinas. We also discuss the importance of PIs revealed from animal models and human diseases, and methods to study PI levels both in vitro and in vivo. We propose that future studies should investigate the function and mechanism of activation of PI-modifying enzymes/phosphatases and further unravel PI regulation and function in the different cell types of the retina.

EFFECT OF SUBSTRATE STIFFNESS ON THE STRUCTURE AND FUNCTION OF CELLS

2006 ◽  
Vol 01 (04) ◽  
pp. 401-410 ◽  
Author(s):  
PENELOPE C. GEORGES ◽  
ILYA LEVENTAL ◽  
WILFREDO De JESúS ROJAS ◽  
R. TYLER MILLER ◽  
PAUL A. JANMEY
Keyword(s):  
Cell Structure ◽  
Soft Materials ◽  
Cell Types ◽  
Biological Tissues ◽  
Structure And Function ◽  
Substrate Stiffness ◽  
Filamin A ◽  
Strong Response ◽  
Different Response ◽  
And Function

Most biological tissues are soft viscoelastic materials with elastic moduli ranging from approximately 100 to 100,000 Pa. Recent studies have examined the effect of substrate rigidity on cell structure and function, and many, but not all cell types exhibit a strong response to substrate stiffness. Some blood cells such as platelets and neutrophils have indistinguishable structures on hard and soft materials as long as they are sufficiently adhesive, whereas many cell types, including fibroblasts and endothelial cells spread much more strongly on rigid compared to soft substrates. A few cell types such as neurons appear to extend better on very soft materials. The different response of astrocytes and neurons to the stiffness of their substrate results in preferential growth of neurons on soft gels and astrocytes on hard gels, and suggests that preventing rigidification of damaged central nervous system tissue after injury may have utility in wound healing. How cells sense substrate stiffness is unknown. One candidate protein, filamin A, which responds to externally derived stresses, was tested in melanoma cells. Cells devoid of filamin A retain the ability to sense substrate stiffness, suggesting that other proteins are required for stiffness sensing.

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