scholarly journals Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist

2020 ◽  
Vol 295 (6) ◽  
pp. 1743-1753 ◽  
Author(s):  
Caleigh M. Azumaya ◽  
Emily A. Linton ◽  
Caitlin J. Risener ◽  
Terunaga Nakagawa ◽  
Erkan Karakas
Keyword(s):  
Calcium Signaling ◽  
Metabolic Diseases ◽  
Inositol Triphosphate ◽  
Biological Processes ◽  
Human Type ◽  
Physiological Processes ◽  
Molecular Determinant ◽  
Specific Regulation ◽  
Type 3

Calcium-mediated signaling through inositol 1,4,5-triphosphate receptors (IP3Rs) is essential for the regulation of numerous physiological processes, including fertilization, muscle contraction, apoptosis, secretion, and synaptic plasticity. Deregulation of IP3Rs leads to pathological calcium signaling and is implicated in many common diseases, including cancer and neurodegenerative, autoimmune, and metabolic diseases. Revealing the mechanism of activation and inhibition of this ion channel will be critical to an improved understanding of the biological processes that are controlled by IP3Rs. Here, we report structural findings of the human type-3 IP3R (IP3R-3) obtained by cryo-EM (at an overall resolution of 3.8 Å), revealing an unanticipated regulatory mechanism where a loop distantly located in the primary sequence occupies the IP3-binding site and competitively inhibits IP3 binding. We propose that this inhibitory mechanism must differ qualitatively among IP3R subtypes because of their diverse loop sequences, potentially serving as a key molecular determinant of subtype-specific calcium signaling in IP3Rs. In summary, our structural characterization of human IP3R-3 provides critical insights into the mechanistic function of IP3Rs and into subtype-specific regulation of these important calcium-regulatory channels.

scholarly journals Metabolomics for Investigating Physiological and Pathophysiological Processes

2019 ◽  
Vol 99 (4) ◽  
pp. 1819-1875 ◽  
Author(s):  
David S. Wishart
Keyword(s):  
Nutrient Sensing ◽  
Biological Processes ◽  
Environmental Sensors ◽  
Major Focus ◽  
Organ Function ◽  
Immune Modulators ◽  
Physiological Processes ◽  
Cellular Energetics ◽  
Wide Perspective

Metabolomics uses advanced analytical chemistry techniques to enable the high-throughput characterization of metabolites from cells, organs, tissues, or biofluids. The rapid growth in metabolomics is leading to a renewed interest in metabolism and the role that small molecule metabolites play in many biological processes. As a result, traditional views of metabolites as being simply the “bricks and mortar” of cells or just the fuel for cellular energetics are being upended. Indeed, metabolites appear to have much more varied and far more important roles as signaling molecules, immune modulators, endogenous toxins, and environmental sensors. This review explores how metabolomics is yielding important new insights into a number of important biological and physiological processes. In particular, a major focus is on illustrating how metabolomics and discoveries made through metabolomics are improving our understanding of both normal physiology and the pathophysiology of many diseases. These discoveries are yielding new insights into how metabolites influence organ function, immune function, nutrient sensing, and gut physiology. Collectively, this work is leading to a much more unified and system-wide perspective of biology wherein metabolites, proteins, and genes are understood to interact synergistically to modify the actions and functions of organelles, organs, and organisms.

scholarly journals A Novel Combined Scientific and Artistic Approach for the Advanced Characterization of Interactomes: The Akirin/Subolesin Model

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 77 ◽  
Author(s):  
Sara Artigas-Jerónimo ◽  
Juan Pastor Comín ◽  
Margarita Villar ◽  
Marinela Contreras ◽  
Pilar Alberdi ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Functional Characterization ◽  
Advanced Characterization ◽  
Research Area ◽  
Dependent Manner ◽  
Biological Processes ◽  
Visual Artists ◽  
Protective Antigens ◽  
Specific Regulation

The main objective of this study was to propose a novel methodology to approach challenges in molecular biology. Akirin/Subolesin (AKR/SUB) are vaccine protective antigens and are a model for the study of the interactome due to its conserved function in the regulation of different biological processes such as immunity and development throughout the metazoan. Herein, three visual artists and a music professor collaborated with scientists for the functional characterization of the AKR2 interactome in the regulation of the NF-κB pathway in human placenta cells. The results served as a methodological proof-of-concept to advance this research area. The results showed new perspectives on unexplored characteristics of AKR2 with functional implications. These results included protein dimerization, the physical interactions with different proteins simultaneously to regulate various biological processes defined by cell type-specific AKR–protein interactions, and how these interactions positively or negatively regulate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in a biological context-dependent manner. These results suggested that AKR2-interacting proteins might constitute suitable secondary transcription factors for cell- and stimulus-specific regulation of NF-κB. Musical perspective supported AKR/SUB evolutionary conservation in different species and provided new mechanistic insights into the AKR2 interactome. The combined scientific and artistic perspectives resulted in a multidisciplinary approach, advancing our knowledge on AKR/SUB interactome, and provided new insights into the function of AKR2–protein interactions in the regulation of the NF-κB pathway. Additionally, herein we proposed an algorithm for quantum vaccinomics by focusing on the model proteins AKR/SUB.

Simulation and characterization of a dual-type 3-dimensional silicon detector

2012 ◽  
Vol 60 (11) ◽  
pp. 1862-1867
Author(s):  
Jihoon Choi ◽  
Kyungmin Lee ◽  
Eunil Won
Keyword(s):  
Silicon Detector ◽  
3 Dimensional ◽  
Type 3

Characterization of human type II procollagen and collagen-specific antibodies and their application to the study of human type II collagen processing and ultrastructure

1997 ◽  
Vol 16 (1) ◽  
pp. 29-39 ◽  
Author(s):  
Sergio A. Jimenez ◽  
Leena Ala-Kokko ◽  
Darwin J. Prockop ◽  
Carmen F. Merryman ◽  
Nora Shepard ◽  
...  
Keyword(s):  
Type Ii Collagen ◽  
Type Ii ◽  
Specific Antibodies ◽  
Human Type

scholarly journals Characterization of a 190-Kilobase Pair Domain of Human Type I Hair Keratin Genes

1998 ◽  
Vol 273 (41) ◽  
pp. 26683-26691 ◽  
Author(s):  
Michael A. Rogers ◽  
Hermelita Winter ◽  
Christian Wolf ◽  
Marina Heck ◽  
Jürgen Schweizer
Keyword(s):  
Type I ◽  
Human Type ◽  
Hair Keratin

FEATURES OF CALCIUM HOMEOSTASIS AND CALCIUM SIGNALING IN NEURONS

Vestnik ◽  
2021 ◽  
pp. 208-214
Author(s):  
Б.К. Кайрат ◽  
С.Т. Тулеуханов ◽  
В.П. Зинченко
Keyword(s):  
Plasma Membrane ◽  
Calcium Signaling ◽  
Calcium Binding ◽  
Intracellular Signaling ◽  
Cell Damage ◽  
Compensatory Mechanisms ◽  
Physiological Processes ◽  
Intracellular Ca ◽  
Ca Ions ◽  
Ca Homeostasis

Ионы Са являются основным мессенджером в регуляции физиологических функций клеток. Внутриклеточном пространстве ионы Ca могут свободно состоянии диффундироваться в различных частях цитоплазмы, в то же время значительное количество Ca в связанном виде накапливается в различных внутриклеточных депо или в составе кальций-связывающих белков. Регуляция физиологических процессов с ионами внутриклеточного Са происходит в диапазоне концентраций 10 М, тогда как концентрация Са во внеклеточном пространстве выше и составляет 10 М, для поддержании градиента концентраций в клетках имеются важные Са транспортирующие системы плазматической мембраны, эндоплазматического ретикулума и митохондрий. В нейронах функционируют внутриклеточные ферменты и белки плазматической мембраны для поддержания Са-гомеостаза и реализации механизмов внутриклеточной сигнализации для обеспечения жизнедеятельности в выживании клеток. Нарушение или гиперактивация одного или нескольких механизмов кальциевой сигнализации может привести к повреждению и гибели нейронов в случае отсутствия компенсаторных механизмов. Ca ions are a key messenger for the regulation of most of the physiological functions of cells. Inside the cell, Ca ions can freely diffuse in various parts of the cytoplasm, but a significant amount of Ca is also bound in various intracellular depots or in the form of calcium-binding proteins. The regulation of physiological processes by intracellular Ca ions occurs in the concentration range of 10 M, and the concentration of Ca in the extracellular space is higher and is 10 M, and to maintain this concentration gradient, cells have Ca-transporting systems of the plasma membrane, endoplasmic reticulum and mitochondria. In neurons, a large number of intracellular enzymes and plasma membrane proteins function to maintain Ca-homeostasis and implement intracellular signaling mechanisms to ensure vital activity in the survival of cells. Violation or hyperactivation of one or more mechanisms of calcium signaling can lead to cell damage and death in the absence of compensatory mechanisms.

scholarly journals Impact of spineless cactus cultivation (O. Ficus-indica) on the thermal characteristics of soil

2018 ◽  
Vol 13 (1) ◽  
pp. 1
Author(s):  
Willames De Albuquerque Soares
Keyword(s):  
Heat Capacity ◽  
Thermal Characteristics ◽  
Thermal Characterization ◽  
Biological Processes ◽  
Volumetric Heat Capacity ◽  
Average Value ◽  
Brazilian Semiarid ◽  
Cultivation Techniques ◽  
Soil Changes

Temperature is a fundamentally important factor for understanding the physical, chemical, and biological processes that occur in soil. However, there are few studies in the Brazilian semiarid zone that seek to understand how soil degradation affects its thermal characteristics. The objective of this study was to evaluate the influence of cultivation techniques on the thermal characterization of soil, using the model proposed by Johansen. The study was conducted in the Agreste region of the state of Pernambuco, Brazil on two plots of land, one with native vegetation (Caatinga) and the other with spineless cactus (O. ficus - indica). It was observed that the procedures used to prepare the soil for cultivation of spineless cactus caused a reduction in the capacity to transmit the surface temperature to the interior of the soil. Changes in the physical properties of the soil required for cultivation resulted in a reduction in the average value of the volumetric heat capacity of about 22%; an increase of approximately 5% in the average volumetric heat capacity and a 26% increase in the thermal diffusivity of the soil, as well as a reduction of approximately 50% in the heat flux from the surface of the soil.

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