scholarly journals Dynamic and asymmetric fluctuations in the microtubule wall captured by high-resolution cryoelectron microscopy

2020 ◽  
Vol 117 (29) ◽  
pp. 16976-16984 ◽  
Author(s):  
Garrett E. Debs ◽  
Michael Cha ◽  
Xueqi Liu ◽  
Andrew R. Huehn ◽  
Charles V. Sindelar
Keyword(s):  
High Resolution ◽  
Dynamic Properties ◽  
Structural Level ◽  
Structural Polymorphism ◽  
Helical Symmetry ◽  
Refinement Method ◽  
Single Subunit ◽  
Existing Structure ◽  
Hinge Angle

Microtubules are tubular polymers with essential roles in numerous cellular activities. Structures of microtubules have been captured at increasing resolution by cryo-EM. However, dynamic properties of the microtubule are key to its function, and this behavior has proved difficult to characterize at a structural level due to limitations in existing structure determination methods. We developed a high-resolution cryo-EM refinement method that divides an imaged microtubule into its constituent protofilaments, enabling deviations from helicity and other sources of heterogeneity to be quantified and corrected for at the single-subunit level. We demonstrate that this method improves the resolution of microtubule 3D reconstructions and substantially reduces anisotropic blurring artifacts, compared with methods that utilize helical symmetry averaging. Moreover, we identified an unexpected, discrete behavior of the m-loop, which mediates lateral interactions between neighboring protofilaments and acts as a flexible hinge between them. The hinge angle adopts preferred values corresponding to distinct conformations of the m-loop that are incompatible with helical symmetry. These hinge angles fluctuate in a stochastic manner, and perfectly cylindrical microtubule conformations are thus energetically and entropically penalized. The hinge angle can diverge further from helical symmetry at the microtubule seam, generating a subpopulation of highly distorted microtubules. However, the seam-distorted subpopulation disappears in the presence of Taxol, a microtubule stabilizing agent. These observations provide clues into the structural origins of microtubule flexibility and dynamics and highlight the role of structural polymorphism in defining microtubule behavior.

Nucleosome dynamics

2006 ◽  
Vol 73 ◽  
pp. 109-119 ◽  
Author(s):  
Chris Stockdale ◽  
Michael Bruno ◽  
Helder Ferreira ◽  
Elisa Garcia-Wilson ◽  
Nicola Wiechens ◽  
...  
Keyword(s):  
High Resolution ◽  
Chromatin Structure ◽  
Current Knowledge ◽  
Dynamic Properties ◽  
Structure And Dynamics ◽  
Nucleosome Dynamics ◽  
Sharp Focus ◽  
Recent Advances ◽  
Insight Into ◽  
Chromatin Structure And Dynamics

In the 30 years since the discovery of the nucleosome, our picture of it has come into sharp focus. The recent high-resolution structures have provided a wealth of insight into the function of the nucleosome, but they are inherently static. Our current knowledge of how nucleosomes can be reconfigured dynamically is at a much earlier stage. Here, recent advances in the understanding of chromatin structure and dynamics are highlighted. The ways in which different modes of nucleosome reconfiguration are likely to influence each other are discussed, and some of the factors likely to regulate the dynamic properties of nucleosomes are considered.

Quantitative accuracy of serotonergic neurotrans-mission imaging with high-resolution 123I SPECT

2004 ◽  
Vol 43 (06) ◽  
pp. 185-189 ◽  
Author(s):  
J. T. Kuikka
Keyword(s):  
High Resolution ◽  
Scatter Correction ◽  
Region Of Interest ◽  
Binding Potential ◽  
Partial Volume ◽  
Therapeutic Drugs ◽  
Quantitative Accuracy ◽  
Critical Error ◽  
Statistical Noise

Summary Aim: Serotonin transporter (SERT) imaging can be used to study the role of regional abnormalities of neurotransmitter release in various mental disorders and to study the mechanism of action of therapeutic drugs or drugs’ abuse. We examine the quantitative accuracy and reproducibility that can be achieved with high-resolution SPECT of serotonergic neurotransmission. Method: Binding potential (BP) of 123I labeled tracer specific for midbrain SERT was assessed in 20 healthy persons. The effects of scatter, attenuation, partial volume, mis-registration and statistical noise were estimated using phantom and human studies. Results: Without any correction, BP was underestimated by 73%. The partial volume error was the major component in this underestimation whereas the most critical error for the reproducibility was misplacement of region of interest (ROI). Conclusion: The proper ROI registration, the use of the multiple head gamma camera with transmission based scatter correction introduce more relevant results. However, due to the small dimensions of the midbrain SERT structures and poor spatial resolution of SPECT, the improvement without the partial volume correction is not great enough to restore the estimate of BP to that of the true one.

Which is the role of dynamic high-resolution ultrasound (D-HRUS) in the assessment of plantar plate tears?

2008 ◽  
Vol 29 (S 1) ◽  
Author(s):  
LM Sconfienza ◽  
F Lacelli ◽  
G Grillo ◽  
G Serafini ◽  
G Garlaschi ◽  
...  
Keyword(s):  
High Resolution ◽  
Plantar Plate

High-Resolution CT in Paraquat Poisoning of the Lung: Role of Prognosis Prediction

1998 ◽  
Vol 38 (6) ◽  
pp. 1027
Author(s):  
Kyoung Suk Kim ◽  
Young Tong Kim ◽  
Eun Joo Kwon ◽  
Choung Sik Choi ◽  
Han Heag Im ◽  
...  
Keyword(s):  
High Resolution ◽  
Prognosis Prediction ◽  
High Resolution Ct ◽  
Paraquat Poisoning

scholarly journals The Role of High-Resolution Analytical Techniques in the Development of Functional Foods

2021 ◽  
Vol 22 (6) ◽  
pp. 3220
Author(s):  
Álvaro Fernández-Ochoa ◽  
Francisco Javier Leyva-Jiménez ◽  
María De la Luz Cádiz-Gurrea ◽  
Sandra Pimentel-Moral ◽  
Antonio Segura-Carretero
Keyword(s):  
High Resolution ◽  
Functional Foods ◽  
Intervention Studies ◽  
Analytical Techniques ◽  
Nutritional Intervention ◽  
Bioactive Properties ◽  
Metabolic Reactions ◽  
Bioactive Potential ◽  
Endogenous Metabolites

The approaches based on high-resolution analytical techniques, such as nuclear magnetic resonance or mass spectrometry coupled to chromatographic techniques, have a determining role in several of the stages necessary for the development of functional foods. The analyses of botanical extracts rich in bioactive compounds is one of the fundamental steps in order to identify and quantify their phytochemical composition. However, the compounds characterized in the extracts are not always responsible for the bioactive properties because they generally undergo metabolic reactions before reaching the therapeutic targets. For this reason, analytical techniques are also applied to analyze biological samples to know the bioavailability, pharmacokinetics and/or metabolism of the compounds ingested by animal or human models in nutritional intervention studies. In addition, these studies have also been applied to determine changes of endogenous metabolites caused by prolonged intake of compounds with bioactive potential. This review aims to describe the main types and modes of application of high-resolution analytical techniques in all these steps for functional food development.

scholarly journals System-wide identification and prioritization of enzyme substrates by thermal analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amir Ata Saei ◽  
Christian M. Beusch ◽  
Pierre Sabatier ◽  
Juan Astorga Wells ◽  
Hassan Gharibi ◽  
...  
Keyword(s):  
Thermal Analysis ◽  
Thioredoxin Reductase ◽  
Structural Level ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Enzyme Substrate ◽  
Thioredoxin Reductase 1 ◽  
Enzyme Substrates ◽  
Substrate Proteins

AbstractDespite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.

scholarly journals Reopening Selves: Phenomenological Considerations on Psychiatric Spaces and the Therapeutic Stance

2021 ◽  
pp. 1-12
Author(s):  
Samuel Thoma ◽  
Isabelle Schwänzl ◽  
Laura Galbusera
Keyword(s):  
Social Factors ◽  
Phenomenological Research ◽  
Social World ◽  
Societal Implications ◽  
Structural Level ◽  
Open Door ◽  
Coercive Treatment ◽  
Psychiatric Institutions ◽  
The Individual

Classical and contemporary phenomenological approaches in psychiatry describe schizophrenia as a disorder of common sense and self-affection. Although taking into account intersubjectivity, this conceptualization still puts forward an individualistic view of the disorder, that is, the intersubjective deficit resides within the person. To overcome such individualism, in this article, we first propose that schizophrenic experience might be understood as arising from a dialectic relation between the self’s loss of openness to the world and the world’s loss of openness to the self. To show the relevance of social factors at the onset of schizophrenic experience, we propose a phenomenological analysis of trigger situations. In the second and main part of this article, we then focus on the implications of these phenomenological insights for the clinical practice: we argue that if schizophrenia is understood as a loss of openness between self and social world, psychiatric institutions should be transformed into spaces that enable a reopening of selves. We first describe <i>enclosing</i> phenomena such as coercive treatment to then, in contrast, present particular forms of <i>open psychiatric spaces</i> such as open door approaches and open dialogue. Besides the institutional-structural level, we also highlight aspects of openness at the intersubjective level of the individual agents, thus particularly emphasizing the role of an open therapeutic stance. We thus speak of (re)opening <i>selves</i> as we believe that the reopening of the patients’ self cannot but be related to and fostered by a reopening of the professionals’ self and stance. We thus argue that openness in the therapeutic stance is key to initiating the further process of recovery, which we describe as a reattunement of selves both at the bodily and narrative level. Last but not least, we sketch out possibilities for future phenomenological research on the question of psychiatric space and draw some broader societal implications.

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