scholarly journals Proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy: potential targets in calcium regulatory network

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leila Sadeghi ◽  
Albert Anatolyevich Rizvanov ◽  
Bahareh Dabirmanesh ◽  
Ilnur Ildusovich Salafutdinov ◽  
Mohammad Sayyah ◽  
...  
Keyword(s):  
Calcium Influx ◽  
Epileptic Seizures ◽  
Rat Hippocampus ◽  
Proteomic Profiling ◽  
Laser Desorption Mass Spectrometry ◽  
Adp Ribosyl Cyclase ◽  
Molecular Events ◽  
Wide Range ◽  
Effective Role ◽  
Models Of Epilepsy

AbstractHerein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spectrometry were identified across the rat models of epilepsy. Based on network analysis, the majority of differentially expressed proteins were associated with Ca2+ homeostasis. Changes in ADP-ribosyl cyclase (ADPRC), lysophosphatidic acid receptor 3 (LPAR3), calreticulin, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), synaptosomal nerve-associated protein 25 (SNAP 25) and transgelin 3 proteins were probed by Western blot analysis and validated using immunohistochemistry. Inhibition of calcium influx by 8-Bromo-cADP-Ribose (8-Br-cADPR) and 2-Aminoethyl diphenylborinate (2-APB) which act via the ADPRC and LPAR3, respectively, attenuated epileptic seizures. Considering a wide range of molecular events and effective role of calcium homeostasis in epilepsy, polypharmacy with multiple realistic targets should be further explored to reach the most effective treatments.

scholarly journals Integrative ‘Omic’ Approach Towards Understanding the Nature of Human Diseases

2012 ◽  
Vol 15 (Supplement) ◽  
pp. 45-50 ◽  
Author(s):  
Borut Peterlin ◽  
A Maver
Keyword(s):  
Large Body ◽  
Experimental Information ◽  
Cellular Level ◽  
Human Diseases ◽  
Sequence Information ◽  
Proteomic Profiling ◽  
Disease Etiology ◽  
Complete Representation ◽  
Molecular Alterations ◽  
Molecular Events

ABSTRACT The combination of improving technologies for molecular interrogation of global molecular alterations in human diseases along with increases in computational capacity, have enabled unprecedented insight into disease etiology, pathogenesis and have enabled new possibilities for biomarker development. A large body of data has accumulated over recent years, with a most prominent increase in information originating from genomic, transcriptomic and proteomic profiling levels. However, the complexity of the data made discovery of highorder disease mechanisms involving various biological layers, difficult, and therefore required new approaches toward integration of such data into a complete representation of molecular events occurring on cellular level. For this reason, we developed a new mode of integration of results coming from heterogeneous origins, using rank statistics of results from each profiling level. Due to the increased use of nextgeneration sequencing technology, experimental information is becoming increasingly more associated to sequence information, for which reason we have decided to synthesize the heterogeneous results using the information of their genomic position. We therefore propose a novel positional integratomic approach toward studying ‘omic’ information in human disease.

Pregnant Occupant Model Including a Fetus for Vehicle Safety Investigations

2014 ◽  
Author(s):  
B. Serpil Acar ◽  
M. Moustafa ◽  
Volkan Esat ◽  
Memis Acar
Keyword(s):  
Finite Element ◽  
Road Safety ◽  
Vehicle Safety ◽  
Head Model ◽  
Frontal Impacts ◽  
Wide Range ◽  
Realistic Representation ◽  
Effective Role ◽  
Loading Tests ◽  
Occupant Modelling

Computational occupant modelling has an effective role to play in investigating road safety. Realistic representation of occupants is very important to make investigations in virtual environment. Pregnant occupant modelling can help investigating safety for unborn occupants (fetuses) however, existing pregnant occupant models are not very realistic. Most do not anthropometrically represent pregnant women and do not include a fetus model. ‘Expecting’, a computational pregnant occupant model, developed with a view to simulate the dynamic response to crash impacts is briefly explained in this paper. The model is validated through rigid bar impacts and belt loading tests and used to simulate a wide range of impacts. ‘Expecting’, possess the anthropometric properties of a 5th percentile female at around the 38th week of pregnancy. The model is complete with a finite element uterus and a realistic multibody fetus which is a novel feature in models of this kind. In this paper, the effect of further developments to ‘Expecting’, by incorporating a finite element fetus head model is investigated. Further detailed anatomic geometry is used to generate deformable fetus head model. The model is used to simulate a range of frontal impacts with seatbelt and airbag, as well as no restraint cases. The strains developed in the utero-placental interface are used as the main criteria for fetus safety. The effect of incorporating a finite element fetus head in the pregnant occupant model is discussed.

scholarly journals Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽  
2020 ◽  
Author(s):  
Kaitlyn A Dorsett ◽  
Michael P Marciel ◽  
Jihye Hwang ◽  
Katherine E Ankenbauer ◽  
Nikita Bhalerao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Sialic Acids ◽  
Invasion Resistance ◽  
Cell Behaviors ◽  
Molecular Events ◽  
Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

scholarly journals DDR1 autophosphorylation is a result of aggregation into dense clusters

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
David S. Corcoran ◽  
Victoria Juskaite ◽  
Yuewei Xu ◽  
Frederik Görlitz ◽  
Yuriy Alexandrov ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Receptor Tyrosine Kinase ◽  
Kinase Activity ◽  
Super Resolution ◽  
Activation Kinetics ◽  
Molecular Events ◽  
Wide Range ◽  
Human Disorders ◽  
Resolution Imaging ◽  
Collagen Receptor

AbstractThe collagen receptor DDR1 is a receptor tyrosine kinase that promotes progression of a wide range of human disorders. Little is known about how ligand binding triggers DDR1 kinase activity. We previously reported that collagen induces DDR1 activation through lateral dimer association and phosphorylation between dimers, a process that requires specific transmembrane association. Here we demonstrate ligand-induced DDR1 clustering by widefield and super-resolution imaging and provide evidence for a mechanism whereby DDR1 kinase activity is determined by its molecular density. Ligand binding resulted in initial DDR1 reorganisation into morphologically distinct clusters with unphosphorylated DDR1. Further compaction over time led to clusters with highly aggregated and phosphorylated DDR1. Ligand-induced DDR1 clustering was abolished by transmembrane mutations but did not require kinase activity. Our results significantly advance our understanding of the molecular events underpinning ligand-induced DDR1 kinase activity and provide an explanation for the unusually slow DDR1 activation kinetics.

The Biochemistry and Molecular Biology of Starch Synthesis in Cereals

1995 ◽  
Vol 22 (4) ◽  
pp. 647 ◽  
Author(s):  
MK Morell ◽  
S Rahman ◽  
SL Abrahams ◽  
R Appels
Keyword(s):  
Molecular Biology ◽  
Starch Synthesis ◽  
Industrial Applications ◽  
Molecular Structures ◽  
End User ◽  
Biochemical Processes ◽  
Starch Quality ◽  
Molecular Events ◽  
Wide Range ◽  
Broad Outline

Starch is a key constituent of plant products finding utility as both a major component of a wide range of staple and processed foods, and as a feedstock for industrial processes. While there has traditionally been a focus on the quantity of starch production, starch quality is of increasing importance to the end-user as consumer demands become more sophisticated and as the range of industrial applications of starch broadens. Determinants of starch quality include the amylose to amylopectin ratio, the distribution of molecular structures within these fractions, and the packaging of the starch in granules. The biochemical processes involved in the transformation of the sucrose delivered to the endosperm cytosol to starch in the amyloplast are understood in broad outline. The importance of particular isoenzymes or processes to the production of starches of specific structures are, however, not well understood. This paper reviews aspects of the physiology, biochemistry and molecular biology of starch in plants, with an emphasis on the synthesis of starch in the cereal endosperm. Progress in understanding the linkages between the molecular events in starch synthesis and developing strategies for the manipulation of starch quantity and quality in cereals are discussed.

Proteomic profiling of the insoluble fractions in the rat hippocampus post-propofol anesthesia

2009 ◽  
Vol 465 (2) ◽  
pp. 165-170 ◽  
Author(s):  
Xuena Zhang ◽  
Yang Liu ◽  
Chunsheng Feng ◽  
Shuguang Yang ◽  
Yun Wang ◽  
...  
Keyword(s):  
Rat Hippocampus ◽  
Proteomic Profiling

scholarly journals Designing Patient-Specific Optimal Neurostimulation Patterns for Seizure Suppression

2018 ◽  
Vol 30 (5) ◽  
pp. 1180-1208 ◽  
Author(s):  
Roman A. Sandler ◽  
Kunling Geng ◽  
Dong Song ◽  
Robert E. Hampson ◽  
Mark R. Witcher ◽  
...  
Keyword(s):  
Global Optimization ◽  
Closed Loop ◽  
Epileptic Seizures ◽  
Patient Specific ◽  
Spontaneous Seizure ◽  
Global Optimization Algorithm ◽  
Neuron Network ◽  
Seizure State ◽  
Wide Range ◽  
Stimulation Pattern

Neurostimulation is a promising therapy for abating epileptic seizures. However, it is extremely difficult to identify optimal stimulation patterns experimentally. In this study, human recordings are used to develop a functional 24 neuron network statistical model of hippocampal connectivity and dynamics. Spontaneous seizure-like activity is induced in silico in this reconstructed neuronal network. The network is then used as a testbed to design and validate a wide range of neurostimulation patterns. Commonly used periodic trains were not able to permanently abate seizures at any frequency. A simulated annealing global optimization algorithm was then used to identify an optimal stimulation pattern, which successfully abated 92% of seizures. Finally, in a fully responsive, or closed-loop, neurostimulation paradigm, the optimal stimulation successfully prevented the network from entering the seizure state. We propose that the framework presented here for algorithmically identifying patient-specific neurostimulation patterns can greatly increase the efficacy of neurostimulation devices for seizures.

scholarly journals The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins

2017 ◽  
Vol 63 (4) ◽  
pp. 316-320
Author(s):  
O.A. Buneeva ◽  
A.T. Kopylov ◽  
L.N. Nerobkova ◽  
I.G. Kapitsa ◽  
V.G. Zgoda ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Open Field Test ◽  
Regulation Of Gene Expression ◽  
Control Level ◽  
Mammalian Brain ◽  
Control Group ◽  
Proteomic Profiling ◽  
Dose Administration ◽  
Wide Range ◽  
Mptp Administration

Isatin (indole-2,3-dione) is an endogenous indole found in the mammalian brain, peripheral organs and body fluids. It acts as a neuroprotector, which decreases manifestation of locomotor impairments in animal models of Parkinson's disease. A wide range of biological activity of isatin is associated with interaction of this regulator with numerous isatin-binding proteins. The aim of this study was to investigate the profile of brain isatin-binding proteins in mice with MPTP-induced Parkinsonism (90 min and seven days after administration of this neurotoxin). A single dose administration of MPTP (30 mg/kg, ip.) was accompanied by locomotor impairments in the open field test 90 min after administration; seven days after MPTP administration locomotor activity of mice significantly improved but did not reach the control level. Five independent experiments on proteomic profiling of isatin-binding proteins resulted in confident identification of 96±12 proteins. Development of MPTP-induced locomotor impairments was accompanied by a significant decrease in the number of isatin-binding proteins (63±6; n=5; p<0.01). Seven days after MPTP administration the total number of identified proteins increased and reached the control level (132±34; n=4). The profiles of isatin-binding proteins were rather specific for each group of mice: in the control group these proteins (which were not found in both groups of MPTP-treated mice) represented more than 70% of total proteins. In the case of MPTP treated mice this parameter was 60% (90 min after MPTP administration) and >82% (seven days after MPTP administration). The major changes were found in the groups of isatin-binding proteins involved into cytoskeleton formation and exocytosis, regulation of gene expression, cell division and differentiation and also proteins involved in signal transduction.

scholarly journals Wnt11/Fzd7 signaling compartmentalizes AKAP2/PKA to regulate L-type Ca2+ channel

2019 ◽  
Author(s):  
Kitti D. Csályi ◽  
Tareck Rharass ◽  
Maike Schulz ◽  
Mai H.Q. Phan ◽  
Paulina Wakula ◽  
...  
Keyword(s):  
Heart Development ◽  
Calcium Influx ◽  
Electrical Coupling ◽  
Proteolytic Processing ◽  
Adrenergic Stimulation ◽  
Systematic Analysis ◽  
Physiological Processes ◽  
C Terminus ◽  
Anchoring Proteins ◽  
Wide Range

AbstractCalcium influx through the voltage-gated L-type calcium channels (LTCC) mediates a wide range of physiological processes from contraction to secretion. Despite extensive research on regulation of LTCC conductance by PKA phosphorylation in response to β-adrenergic stimulation, the science remains incomplete. Here, we show that Wnt11, a non-canonical Wnt ligand, through its G protein-coupled receptor (GPCR) Fzd7 attenuates the LTCC conductance by preventing the proteolytic processing of its C terminus. This is mediated across species by protein kinase A (PKA), which is compartmentalized by A-kinase anchoring proteins (AKAP). Systematic analysis of all AKAP family members revealed AKAP2 anchoring of PKA is central to the Wnt11-dependent regulation of the channel. The identified Wnt11/AKAP2/PKA signalosome is required for heart development, controlling the intercellular electrical coupling in the developing zebrafish heart. Altogether, our data revealed Wnt11/Fzd7 signaling via AKAP2/PKA as a conserved alternative GPCR system regulating Ca2+ homeostasis.

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