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 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 O-GlcNAcylation is a key regulator of multiple cellular metabolic pathways

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11443
Author(s):  
Hongshuo Zhang ◽  
Zhen Li ◽  
Yufei Wang ◽  
Ying Kong
Keyword(s):  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Nutrient Sensing ◽  
Molecular Networks ◽  
Biological Processes ◽  
Metabolic Processes ◽  
Metabolic Signaling ◽  
Important Indicator ◽  
Physiological Processes ◽  
Mitochondrial Oxidation

O-GlcNAcylation modifies proteins in serine or threonine residues in the nucleus, cytoplasm, and mitochondria. It regulates a variety of cellular biological processes and abnormal O-GlcNAcylation is associated with diabetes, cancer, cardiovascular disease, and neurodegenerative diseases. Recent evidence has suggested that O-GlcNAcylation acts as a nutrient sensor and signal integrator to regulate metabolic signaling, and that dysregulation of its metabolism may be an important indicator of pathogenesis in disease. Here, we review the literature focusing on O-GlcNAcylation regulation in major metabolic processes, such as glucose metabolism, mitochondrial oxidation, lipid metabolism, and amino acid metabolism. We discuss its role in physiological processes, such as cellular nutrient sensing and homeostasis maintenance. O-GlcNAcylation acts as a key regulator in multiple metabolic processes and pathways. Our review will provide a better understanding of how O-GlcNAcylation coordinates metabolism and integrates molecular networks.

Fluorescent potentiometric dyes for membrane-potential imaging

1994 ◽  
Vol 52 ◽  
pp. 166-167
Author(s):  
Leslie M. Loew
Keyword(s):  
Membrane Potential ◽  
Single Cells ◽  
Quantitative Imaging ◽  
Optical Recording ◽  
Biological Processes ◽  
Major Focus ◽  
The Past ◽  
Excitable Systems ◽  
Major Application ◽  
The Impact

A major application of potentiometric dyes has been the multisite optical recording of electrical activity in excitable systems. After being championed by L.B. Cohen and his colleagues for the past 20 years, the impact of this technology is rapidly being felt and is spreading to an increasing number of neuroscience laboratories. A second class of experiments involves using dyes to image membrane potential distributions in single cells by digital imaging microscopy - a major focus of this lab. These studies usually do not require the temporal resolution of multisite optical recording, being primarily focussed on slow cell biological processes, and therefore can achieve much higher spatial resolution. We have developed 2 methods for quantitative imaging of membrane potential. One method uses dual wavelength imaging of membrane-staining dyes and the other uses quantitative 3D imaging of a fluorescent lipophilic cation; the dyes used in each case were synthesized for this purpose in this laboratory.

scholarly journals Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan H. Trager ◽  
Emanuelle Rizk ◽  
Sharon Rose ◽  
Kuixi Zhu ◽  
Branden Lau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Distinct Pattern ◽  
Study Endpoint ◽  
Inflammatory Gene Expression ◽  
Immune Modulators ◽  
Actinic Keratoses ◽  
Before And After ◽  
Pre Treatment

AbstractThe presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p < 0.0001). Post-imiquimod therapy, levels of CDK1, CXCL13, IL1B, GADPH, TTK, ILF3, EWSR1, BIRC5, PLAUR, ISG20, and C1QBP were significantly lower (adjusted p < 0.05). Complete responders (CR) exhibited a distinct pattern of inflammatory gene expression pre-treatment relative to incomplete responders (IR), with alterations in 15 inflammatory pathways (p < 0.05) reflecting differential expression of 103 genes (p < 0.05). Presence of adverse effects was associated with improved treatment response. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treament may play a part in regression of AKs. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy.

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.

scholarly journals Characterization of the biological processes shaping the genetic structure of the Italian population

BMC Genetics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Silvia Parolo ◽  
Antonella Lisa ◽  
Davide Gentilini ◽  
Anna Maria Di Blasio ◽  
Simona Barlera ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Italian Population ◽  
Biological Processes

scholarly journals Hidden in plain sight: What remains to be discovered in the eukaryotic proteome?

2018 ◽  
Author(s):  
Valerie Wood ◽  
Antonia Lock ◽  
Midori A. Harris ◽  
Kim Rutherford ◽  
Jürg Bähler ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Fission Yeast ◽  
Genome Sequencing ◽  
Large Scale ◽  
Biological Process ◽  
Blind Spot ◽  
Model Organisms ◽  
Biological Processes ◽  
Health And Disease

AbstractThe first decade of genome sequencing stimulated an explosion in the characterization of unknown proteins. More recently, the pace of functional discovery has slowed, leaving around 20% of the proteins even in well-studied model organisms without informative descriptions of their biological roles. Remarkably, many uncharacterized proteins are conserved from yeasts to human, suggesting that they contribute to fundamental biological processes. To fully understand biological systems in health and disease, we need to account for every part of the system. Unstudied proteins thus represent a collective blind spot that limits the progress of both basic and applied biosciences.We use a simple yet powerful metric based on Gene Ontology (GO) biological process terms to define characterized and uncharacterized proteins for human, budding yeast, and fission yeast. We then identify a set of conserved but unstudied proteins in S. pombe, and classify them based on a combination of orthogonal attributes determined by large-scale experimental and comparative methods. Finally, we explore possible reasons why these proteins remain neglected, and propose courses of action to raise their profile and thereby reap the benefits of completing the catalog of proteins’ biological roles.

scholarly journals RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective

2021 ◽  
Vol 22 (19) ◽  
pp. 10285
Author(s):  
Pietro Laneve ◽  
Paolo Tollis ◽  
Elisa Caffarelli
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Potential Role ◽  
Noncoding Rnas ◽  
Rna Metabolism ◽  
Biological Processes ◽  
Diagnostic Biomarkers ◽  
Defective Rna ◽  
Almost All ◽  
Lateral Sclerosis

RNA metabolism is central to cellular physiopathology. Almost all the molecular pathways underpinning biological processes are affected by the events governing the RNA life cycle, ranging from transcription to degradation. The deregulation of these processes contributes to the onset and progression of human diseases. In recent decades, considerable efforts have been devoted to the characterization of noncoding RNAs (ncRNAs) and to the study of their role in the homeostasis of the nervous system (NS), where they are highly enriched. Acting as major regulators of gene expression, ncRNAs orchestrate all the steps of the differentiation programs, participate in the mechanisms underlying neural functions, and are crucially implicated in the development of neuronal pathologies, among which are neurodegenerative diseases. This review aims to explore the link between ncRNA dysregulation and amyotrophic lateral sclerosis (ALS), the most frequent motoneuron (MN) disorder in adults. Notably, defective RNA metabolism is known to be largely associated with this pathology, which is often regarded as an RNA disease. We also discuss the potential role that these transcripts may play as diagnostic biomarkers and therapeutic targets.

scholarly journals Molecular Characterization of a Novel Cathepsin L in Macrobrachium nipponense and Its Function in Ovary Maturation

2022 ◽  
Vol 12 ◽  
Author(s):  
Sufei Jiang ◽  
Yiwei Xiong ◽  
Wenyi Zhang ◽  
Junpeng Zhu ◽  
Dan Cheng ◽  
...  
Keyword(s):  
Cathepsin L ◽  
Cysteine Proteases ◽  
Macrobrachium Nipponense ◽  
Reading Frame ◽  
Physiological Processes ◽  
Gonad Somatic Index ◽  
Oriental River Prawn ◽  
Ovary Maturation

Cathepsin L genes, which belonged to cysteine proteases, were a series of multifunctional protease and played important roles in a lot of pathological and physiological processes. In this study, we analyzed the characteristics a cathepsin L (named Mn-CL2) in the female oriental river prawn, Macrobrachium nipponense which was involved in ovary maturation. The Mn-CL2 was1,582 bp in length, including a 978 bp open reading frame that encoded 326 amino acids. The Mn-CL2 was classified into the cathepsin L group by phylogenetic analysis. Real-time PCR (qPCR) analysis indicated that Mn-CL2 was highly expressed in the hepatopancreas and ovaries of female prawns. During the different ovarian stages, Mn-CL2 expression in the hepatopancreas and ovaries peaked before ovarian maturation. In situ hybridization studies revealed that Mn-CL2 was localized in the oocyte of the ovary. Injection of Mn-CL2 dsRNA significantly reduced the expression of vitellogenin. Changes in the gonad somatic index also confirmed the inhibitory effects of Mn-CL2 dsRNA on ovary maturation. These results suggest that Mn-CL2 has a key role in promoting ovary maturation.

scholarly journals Chromatin accessibility is dynamically regulated across C. elegans development and ageing

2018 ◽  
Author(s):  
Jürgen Jänes ◽  
Yan Dong ◽  
Michael Schoof ◽  
Jacques Serizay ◽  
Alex Appert ◽  
...  
Keyword(s):  
Regulatory Mechanism ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Protein Coding ◽  
C Elegans ◽  
Transcription Profiles ◽  
Physiological Processes ◽  
Global Identification ◽  
Identification And Characterization

AbstractAn essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,714 protein-coding promoters and 19,231 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, hundreds of promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements is regulated during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing.

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