scholarly journals Uncovering Discrete Synaptic Proteomes to Understand Neurological Disorders

Proteomes ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 30 ◽  
Author(s):  
Yi-Zhi Wang ◽  
Jeffrey Savas
Keyword(s):  
Neurological Disorders ◽  
Neuronal Cell ◽  
Protein Composition ◽  
Cell Junctions ◽  
Neuronal Populations ◽  
Wide Range ◽  
Averaging Problem ◽  
Analysis Strategies ◽  
Neuronal Types ◽  
New Strategies

The mammalian nervous system is an immensely heterogeneous organ composed of a diverse collection of neuronal types that interconnect in complex patterns. Synapses are highly specialized neuronal cell-cell junctions with common and distinct functional characteristics that are governed by their protein composition or synaptic proteomes. Even a single neuron can possess a wide-range of different synapse types and each synapse contains hundreds or even thousands of proteins. Many neurological disorders and diseases are caused by synaptic dysfunction within discrete neuronal populations. Mass spectrometry (MS)-based proteomic analysis has emerged as a powerful strategy to characterize synaptic proteomes and potentially identify disease driving synaptic alterations. However, most traditional synaptic proteomic analyses have been limited by molecular averaging of proteins from multiple types of neurons and synapses. Recently, several new strategies have emerged to tackle the ‘averaging problem’. In this review, we summarize recent advancements in our ability to characterize neuron-type specific and synapse-type specific proteomes and discuss strengths and limitations of these emerging analysis strategies.

scholarly journals Advanced Microfluidic Technologies for Lipid Nano-Microsystems from Synthesis to Biological Application

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 141
Author(s):  
Bruna Carvalho ◽  
Bruno Ceccato ◽  
Mariano Michelon ◽  
Sang Han ◽  
Lucimara de la Torre
Keyword(s):  
Lipid Nanoparticles ◽  
Future Trends ◽  
Biological Applications ◽  
Biological Application ◽  
Shell Nanoparticles ◽  
Cellular Environment ◽  
Wide Range ◽  
Core Shell Nanoparticles ◽  
New Strategies ◽  
Lipid Structures

Microfluidics is an emerging technology that can be employed as a powerful tool for designing lipid nano-microsized structures for biological applications. Those lipid structures can be used as carrying vehicles for a wide range of drugs and genetic materials. Microfluidic technology also allows the design of sustainable processes with less financial demand, while it can be scaled up using parallelization to increase production. From this perspective, this article reviews the recent advances in the synthesis of lipid-based nanostructures through microfluidics (liposomes, lipoplexes, lipid nanoparticles, core-shell nanoparticles, and biomimetic nanovesicles). Besides that, this review describes the recent microfluidic approaches to produce lipid micro-sized structures as giant unilamellar vesicles. New strategies are also described for the controlled release of the lipid payloads using microgels and droplet-based microfluidics. To address the importance of microfluidics for lipid-nanoparticle screening, an overview of how microfluidic systems can be used to mimic the cellular environment is also presented. Future trends and perspectives in designing novel nano and micro scales are also discussed herein.

scholarly journals The fall and rise of consciousness science

2018 ◽  
Author(s):  
Anil Seth
Keyword(s):  
Twentieth Century ◽  
Empirical Study ◽  
Neurological Disorders ◽  
Neural Mechanisms ◽  
Central Feature ◽  
Hard Problem ◽  
Physical Processes ◽  
Wide Range ◽  
Third Person ◽  
The Universe

At the birth of psychology as a science, consciousness was its central problem. But throughout the twentieth century, ideological and methodological concerns pushed the explicit empirical study of consciousness to the sidelines. Since the 1990s, studying consciousness has regained a legitimacy and impetus befitting its status as the central feature of our mental lives. Nowadays consciousness science encompasses a rich interdisciplinary mixture drawing together philosophical, theoretical, computational, experimental, and clinical perspectives. While solving the metaphysically ‘hard’ problem of why consciousness is part of the universe may seem as intractable as ever, scientists have learned a great deal about the neural mechanisms underlying conscious states. Further progress will depend on specifying closer explanatory mappings between (first person subjective) phenomenological descriptions and (third person objective) descriptions of biological and physical processes. Such progress will help reframe our understanding of our place in nature, and may also accelerate clinical approaches to a wide range of psychiatric and neurological disorders.

scholarly journals Obtaining human hair keratin-based films and their characteristics

2021 ◽  
Vol 15 (1) ◽  
pp. 27-36
Author(s):  
V. V. Mykhaliuk ◽  
◽  
V. V. Havryliak ◽  
Keyword(s):  
Molecular Weight ◽  
Disulfide Bonds ◽  
Protein Concentration ◽  
Sodium Dodecyl ◽  
Protein Composition ◽  
Surface Characteristics ◽  
Film Structure ◽  
X Ray ◽  
Wide Range ◽  
Scanning Electron

Background. Keratins are natural biopolymers with a wide range of applications in the field of biotechnology. Materials and Methods. Extraction of keratins was performed by a modified Nakamura method using 250 mM DTT. The protein concentration in the supernatant was determined by Bradford method. The protein composition was studied by their electro­phoretic separation in a polyacrylamide gel in the presence of sodium dodecyl sulfate. The films were made by casting. The surface characteristics of the films were determined using a scanning electron microscope REMMA-102. The elemental composition of the films was determined using an X-ray microanalyzer. Results. The protein concentration in the supernatant was 3.75 mg/mL. After using dithiothreitol in the extraction mixture, we obtained proteins of intermediate filaments with a molecular weight of 40–60 kDa and a low Sulfur content. In the low molecular weight region, we obtained keratin-associated proteins with a molecular weight of 10–30 kDa and a high content of Sulfur. These proteins belong to fibrillar proteins, which can be used as a matrix for the creation of new keratin-containing biocomposites with a wide range of applications in reparative medicine and tissue engineering. Based on the obtained keratin extract, polymer films with and without the addition of glycerol were made. Scanning electron microscopy revealed that glycerol provided the film structure with homogeneity and plasticity due to the accumulation of moisture after the fixation by water vapor. The X-ray microanalysis of films revealed such elements as Sodium, Silicon, Sulfur, Potassium. Among the detected elements, Sulfur has the largest share that is due to the large number of disulfide bonds in the keratin molecule. Conclusions. The polymer keratin films with the addition of glycerol demonstrated better mechanical properties and can be used in biomedicine.

scholarly journals Automated pupillometry to detect command following in neurological patients: a proof-of-concept study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6929 ◽  
Author(s):  
Alexandra Vassilieva ◽  
Markus Harboe Olsen ◽  
Costanza Peinkhofer ◽  
Gitte Moos Knudsen ◽  
Daniel Kondziella
Keyword(s):  
Brain Injury ◽  
Healthy Volunteers ◽  
Neurological Disorders ◽  
Mental Arithmetic ◽  
Proof Of Concept ◽  
Icu Patients ◽  
Wide Range ◽  
Level Of Consciousness ◽  
Neurological Patients ◽  
Command Following

Background Levels of consciousness in patients with acute and chronic brain injury are notoriously underestimated. Paradigms based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) may detect covert consciousness in clinically unresponsive patients but are subject to logistical challenges and the need for advanced statistical analysis. Methods To assess the feasibility of automated pupillometry for the detection of command following, we enrolled 20 healthy volunteers and 48 patients with a wide range of neurological disorders, including seven patients in the intensive care unit (ICU), who were asked to engage in mental arithmetic. Results Fourteen of 20 (70%) healthy volunteers and 17 of 43 (39.5%) neurological patients, including 1 in the ICU, fulfilled prespecified criteria for command following by showing pupillary dilations during ≥4 of five arithmetic tasks. None of the five sedated and unconscious ICU patients passed this threshold. Conclusions Automated pupillometry combined with mental arithmetic appears to be a promising paradigm for the detection of covert consciousness in people with brain injury. We plan to build on this study by focusing on non-communicating ICU patients in whom the level of consciousness is unknown. If some of these patients show reproducible pupillary dilation during mental arithmetic, this would suggest that the present paradigm can reveal covert consciousness in unresponsive patients in whom standard investigations have failed to detect signs of consciousness.

Immortalized neurons for the study of hypothalamic function

2011 ◽  
Vol 300 (5) ◽  
pp. R1030-R1052 ◽  
Author(s):  
Prasad S. Dalvi ◽  
Anaies Nazarians-Armavil ◽  
Stephanie Tung ◽  
Denise D. Belsham
Keyword(s):  
Neuronal Cell ◽  
Glucose Sensing ◽  
T Antigen ◽  
Molecular Techniques ◽  
Cell Models ◽  
Hypothalamic Neurons ◽  
In Vivo Models ◽  
Wide Range ◽  
Hypothalamic Function

The hypothalamus is a vital part of the central nervous system: it harbors control systems implicated in regulation of a wide range of homeostatic processes, including energy balance and reproduction. Structurally, the hypothalamus is a complex neuroendocrine tissue composed of a multitude of unique neuronal cell types that express a number of neuromodulators, including hormones, classical neurotransmitters, and specific neuropeptides that play a critical role in mediating hypothalamic function. However, neuropeptide and receptor gene expression, second messenger activation, and electrophysiological and secretory properties of these hypothalamic neurons are not yet fully defined, primarily because the heterogeneity and complex neuronal architecture of the neuroendocrine hypothalamus make such studies challenging to perform in vivo. To circumvent this problem, our research group recently generated embryonic- and adult-derived hypothalamic neuronal cell models by utilizing the novel molecular techniques of ciliary neurotrophic factor-induced neurogenesis and SV40 T antigen transfer to primary hypothalamic neuronal cell cultures. Significant research with these cell lines has demonstrated their value as a potential tool for use in molecular genetic analysis of hypothalamic neuronal function. Insights gained from hypothalamic immortalized cells used in conjunction with in vivo models will enhance our understanding of hypothalamic functions such as neurogenesis, neuronal plasticity, glucose sensing, energy homeostasis, circadian rhythms, and reproduction. This review discusses the generation and use of hypothalamic cell models to study mechanisms underlying the function of individual hypothalamic neurons and to gain a more complete understanding of the overall physiology of the hypothalamus.

scholarly journals A species-specific nucleosomal signature defines a periodic distribution of amino acids in proteins

Open Biology ◽  
2015 ◽  
Vol 5 (4) ◽  
pp. 140218 ◽  
Author(s):  
Luis Quintales ◽  
Ignacio Soriano ◽  
Enrique Vázquez ◽  
Mónica Segurado ◽  
Francisco Antequera
Keyword(s):  
Amino Acids ◽  
Protein Composition ◽  
Open Reading Frames ◽  
Yeast Genome ◽  
Relative Distribution ◽  
Periodic Distribution ◽  
Wide Range ◽  
Average Distribution ◽  
Species Specific ◽  
High Degree

Nucleosomes are the basic structural units of chromatin. Most of the yeast genome is organized in a pattern of positioned nucleosomes that is stably maintained under a wide range of physiological conditions. In this work, we have searched for sequence determinants associated with positioned nucleosomes in four species of fission and budding yeasts. We show that mononucleosomal DNA follows a highly structured base composition pattern, which differs among species despite the high degree of histone conservation. These nucleosomal signatures are present in transcribed and non-transcribed regions across the genome. In the case of open reading frames, they correctly predict the relative distribution of codons on mononucleosomal DNA, and they also determine a periodicity in the average distribution of amino acids along the proteins. These results establish a direct and species-specific connection between the position of each codon around the histone octamer and protein composition.

The GCN5: its biological functions and therapeutic potentials

2021 ◽  
Vol 135 (1) ◽  
pp. 231-257
Author(s):  
Md. Ezazul Haque ◽  
Md. Jakaria ◽  
Mahbuba Akther ◽  
Duk-Yeon Cho ◽  
In-Su Kim ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Cellular Proliferation ◽  
Chromatin Modification ◽  
Structural Features ◽  
Histone Acetyltransferases ◽  
Epigenetic Landscape ◽  
General Control ◽  
Wide Range ◽  
Lysine Acetyltransferase

Abstract General control non-depressible 5 (GCN5) or lysine acetyltransferase 2A (KAT2A) is one of the most highly studied histone acetyltransferases. It acts as both histone acetyltransferase (HAT) and lysine acetyltransferase (KAT). As an HAT it plays a pivotal role in the epigenetic landscape and chromatin modification. Besides, GCN5 regulates a wide range of biological events such as gene regulation, cellular proliferation, metabolism and inflammation. Imbalance in the GCN5 activity has been reported in many disorders such as cancer, metabolic disorders, autoimmune disorders and neurological disorders. Therefore, unravelling the role of GCN5 in different diseases progression is a prerequisite for both understanding and developing novel therapeutic agents of these diseases. In this review, we have discussed the structural features, the biological function of GCN5 and the mechanical link with the diseases associated with its imbalance. Moreover, the present GCN5 modulators and their limitations will be presented in a medicinal chemistry perspective.

Strategic Exploitation of the Wittig Reaction: Facile Synthesis of Heteroaromatics and Multifunctional Olefins

Synlett ◽  
2018 ◽  
Vol 29 (20) ◽  
pp. 2608-2622 ◽  
Author(s):  
Wenwei Lin ◽  
Praneeth Karanam ◽  
Ganapuram Reddy
Keyword(s):  
Wittig Reaction ◽  
Coumarin Derivatives ◽  
Facile Synthesis ◽  
Diversity Oriented Synthesis ◽  
New Methods ◽  
Intramolecular Wittig Reaction ◽  
New Synthesis ◽  
Wide Range ◽  
Industrial Level ◽  
New Strategies

In this account, our group’s efforts towards exploring new substrates as precursors for the Wittig reaction have been discussed. Several new strategies developed by our group for the generation of requisite ylides for the Wittig reaction are highlighted. The idea behind the development of some chemoselective and diversity-oriented strategies are discussed in detail in a progressive manner. These strategies encompass a wide range of substrates that are employed for the synthesis of an array of heterocycles and multifunctional olefins and present a huge scope for their application on an industrial level.1 Introduction2 Development of New Methods to Effect Intramolecular Wittig Reaction3 Development of a Catalytic Wittig Reaction4 New Synthesis of Bis-Heteroarenes5 Direct β-Acylation of 2-Arylidene-1,3-indandiones6 Doubly Chemoselective Protocol for the Diversity-Oriented Synthesis of Coumarin Derivatives7 Conclusion

scholarly journals Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species

2016 ◽  
Vol 113 (21) ◽  
pp. 6029-6034 ◽  
Author(s):  
Jiang He ◽  
Ruobo Zhou ◽  
Zhuhao Wu ◽  
Monica A. Carrasco ◽  
Peri T. Kurshan ◽  
...  
Keyword(s):  
Glial Cell ◽  
Animal Species ◽  
Homo Sapiens ◽  
Neuronal Cell ◽  
Cell Types ◽  
Membrane Skeleton ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Periodic Distribution ◽  
Neuronal Types

Actin, spectrin, and associated molecules form a periodic, submembrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal- and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: Spectrin shows a long-range, periodic distribution throughout all axons but appears periodic only in a small fraction of dendrites, typically in the form of isolated patches in subregions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is disrupted in most presynaptic boutons but is present in an appreciable fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus, and Homo sapiens.

Alterations in τ Immunostaining in the Rat Hippocampus following Transient Cerebral Ischemia

1994 ◽  
Vol 14 (4) ◽  
pp. 554-564 ◽  
Author(s):  
James W. Geddes ◽  
Claudia Schwab ◽  
Susan Craddock ◽  
Janice L. Wilson ◽  
L. Creed Pettigrew
Keyword(s):  
Neuronal Damage ◽  
Hippocampal Formation ◽  
Molecular Layer ◽  
Neuronal Cell ◽  
Direct Result ◽  
Ischemic Insult ◽  
Vessel Occlusion ◽  
Neuronal Populations ◽  
Neuronal Cell Bodies ◽  
Hilar Neurons

Previous studies in gerbils have shown that cytoskeletal disruption and a loss of the dendritic microtubule-associated protein, MAP2, may occur after short periods of transient global ischemia. τ, a predominantly axonal microtubule-associated protein, has not been examined following ischemia. We compared neuronal damage with alterations in MAP2, τ, and 72-kD heat shock protein (HSP72) immunostaining at various reperfusion times following 20 min of ischemia in the rat four-vessel occlusion model. τ accumulated in neuronal cell bodies throughout the hippocampal formation 30 min to 2 h after the ischemic insult. Perikaryal τ immunostaining was transient in most regions, but persisted in polymorphic hilar neurons. This was accompanied by a loss of immunostaining in the target of many hilar neurons, the inner molecular layer of the dentate gyrus. The same neuronal populations that exhibited increased τ immunostaining of perikarya later displayed an induction of HSP72 immunoreactivity. In contrast, loss of MAP2 immunostaining was not consistently observed before neuronal death and did not correspond to HSP72 induction. The altered τ immunostaining is not the direct result of excitotoxic insult, as intrahippocampal injection of kainic acid did not cause the somal accumulation of τ, but did cause disruption of MAP2 immunostaining. Taken together, the results suggest that the somal accumulation of τ is an early, sensitive, and selective marker of ischemic insult.

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