scholarly journals Structure and mechanism of NALCN-FAM155A-UNC79-UNC80 channel complex

2021 ◽  
Author(s):  
Yunlu Kang ◽  
Lei Chen

NALCN channel mediates sodium leak currents and is important for maintaining proper resting membrane potential. NALCN and FAM155A form the core complex of the channel, the activity of which essentially depends on the presence of both UNC79 and UNC80, two auxiliary proteins. NALCN, FAM155A, UNC79, and UNC80 co-assemble into a large hetero-tetrameric channel complex. Genetic mutations of NALCN channel components lead to neurodevelopmental diseases. However, the structure and mechanism of the intact channel complex remain elusive. Here, we present the cryo-EM structure of the mammalian NALCN-FAM155A-UNC79-UNC80 quaternary complex. The structure showed that UNC79-UNC80 form a large piler-shaped heterodimer which was tethered to the intracellular side of the NALCN channel through tripartite interactions with the cytoplasmic loops of NALCN. Two interactions are essential for proper cell surface localization of NALCN. The other interaction relieves the self-inhibition of NALCN by pulling the auto-inhibitory CTD Interacting Helix (CIH) out of its binding site.

Author(s):  
Daphna Oyserman

Everyone can imagine their future self, even very young children, and this future self is usually positive and education-linked. To make progress toward an aspired future or away from a feared future requires people to plan and take action. Unfortunately, most people often start too late and commit minimal effort to ineffective strategies that lead their attention elsewhere. As a result, their high hopes and earnest resolutions often fall short. In Pathways to Success Through Identity-Based Motivation Daphna Oyserman focuses on situational constraints and affordances that trigger or impede taking action. Focusing on when the future-self matters and how to reduce the shortfall between the self that one aspires to become and the outcomes that one actually attains, Oyserman introduces the reader to the core theoretical framework of identity-based motivation (IBM) theory. IBM theory is the prediction that people prefer to act in identity-congruent ways but that the identity-to-behavior link is opaque for a number of reasons (the future feels far away, difficulty of working on goals is misinterpreted, and strategies for attaining goals do not feel identity-congruent). Oyserman's book goes on to also include the stakes and how the importance of education comes into play as it improves the lives of the individual, their family, and their society. The framework of IBM theory and how to achieve it is broken down into three parts: how to translate identity-based motivation into a practical intervention, an outline of the intervention, and empirical evidence that it works. In addition, the book also includes an implementation manual and fidelity measures for educators utilizing this book to intervene for the improvement of academic outcomes.


Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1152
Author(s):  
Tatyana Kirila ◽  
Anna Smirnova ◽  
Alla Razina ◽  
Andrey Tenkovtsev ◽  
Alexander Filippov

The water–salt solutions of star-shaped six-arm poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines were studied by light scattering and turbidimetry. The core was hexaaza[26]orthoparacyclophane and the arms were poly-2-ethyl-2-oxazine, poly-2-isopropyl-2-oxazine, poly-2-ethyl-2-oxazoline, and poly-2-isopropyl-2-oxazoline. NaCl and N-methylpyridinium p-toluenesulfonate were used as salts. Their concentration varied from 0–0.154 M. On heating, a phase transition was observed in all studied solutions. It was found that the effect of salt on the thermosensitivity of the investigated stars depends on the structure of the salt and polymer and on the salt content in the solution. The phase separation temperature decreased with an increase in the hydrophobicity of the polymers, which is caused by both a growth of the side radical size and an elongation of the monomer unit. For NaCl solutions, the phase separation temperature monotonically decreased with growth of salt concentration. In solutions with methylpyridinium p-toluenesulfonate, the dependence of the phase separation temperature on the salt concentration was non-monotonic with minimum at salt concentration corresponding to one salt molecule per one arm of a polymer star. Poly-2-alkyl-2-oxazine and poly-2-alkyl-2-oxazoline stars with a hexaaza[26]orthoparacyclophane core are more sensitive to the presence of salt in solution than the similar stars with a calix[n]arene branching center.


2021 ◽  
Vol 7 (17) ◽  
pp. eabg4922
Author(s):  
Chunmei Chang ◽  
Xiaoshan Shi ◽  
Liv E. Jensen ◽  
Adam L. Yokom ◽  
Dorotea Fracchiolla ◽  
...  

Selective autophagy of damaged mitochondria, protein aggregates, and other cargoes is essential for health. Cargo initiates phagophore biogenesis, which entails the conjugation of LC3 to phosphatidylethanolamine. Current models suggest that clustered ubiquitin chains on a cargo trigger a cascade from autophagic cargo receptors through the core complexes ULK1 and class III phosphatidylinositol 3-kinase complex I, WIPI2, and the ATG7, ATG3, and ATG12ATG5-ATG16L1 machinery of LC3 lipidation. This was tested using giant unilamellar vesicles (GUVs), GST-Ub4 as a model cargo, the cargo receptors NDP52, TAX1BP1, and OPTN, and the autophagy core complexes. All three cargo receptors potently stimulated LC3 lipidation on GUVs. NDP52- and TAX1BP1-induced LC3 lipidation required all components, but not ULK1 kinase activity. However, OPTN bypassed the ULK1 requirement. Thus, cargo-dependent stimulation of LC3 lipidation is common to multiple autophagic cargo receptors, yet the details of core complex engagement vary between the different receptors.


2013 ◽  
Vol 2013 (1) ◽  
Author(s):  
George Pattison

AbstractNoting Heidegger’s critique of Kierkegaard’s way of relating time and eternity, the paper offers an alternative reading of Kierkegaard that suggests Heidegger has overlooked crucial elements in the Kierkegaardian account. Gabriel Marcel and Sharon Krishek are used to counter Heidegger’s minimizing of the deaths of others and to show how the deaths of others may become integral to our sense of self. This prepares the way for revisiting Kierkegaard’s discourse on the work of love in remembering the dead. Against the criticism that this reveals the absence of the other in Kierkegaardian love, the paper argues that, on the contrary, it shows how Kierkegaard conceives the self as inseparable from the core relationships of love that, despite of death, constitute it as the self that it is.


1999 ◽  
Vol 36 (6) ◽  
pp. 917-943 ◽  
Author(s):  
Olivier Vanderhaeghe ◽  
Christian Teyssier ◽  
Richard Wysoczanski

At the latitude of the Thor-Odin dome, the Shuswap metamorphic core complex exposes a ~15 km thick structural section composed of an upper unit that preserved Mesozoic metamorphism, structures, and cooling ages, separated from the underlying high-grade rocks by low-angle detachment zones. Below the detachments, the core of the complex consists of an amphibolite-facies middle unit overlying a migmatitic lower unit exposed in the core of the Thor-Odin dome. Combined structural and super high resolution ion microprobe (SHRIMP) U-Pb geochronology studies indicate that the pervasive shallowly dipping foliation and east-west lineation developed in the presence of melt during Paleocene time. SHRIMP analyses of complexly zoned zircon grains suggest that the migmatites of the lower unit crystallized at ~56 Ma, and a syntectonic leucogranite at ~60 Ma. We suggest that leucogranite migrated upward from the migmatites through an array of dikes and sills that permeated the middle unit and ponded to form laccoliths spatially related to the detachment zones. The similarity in ages of inherited zircon cores in the two migmatite and the leucogranite samples suggests a genetic link consistent with the structural analysis. Following the crystallization of migmatites, the terrane cooled rapidly, as indicated by argon thermochronology. We propose that exhumation of the core of the Canadian Cordillera during the formation of the Shuswap metamorphic core complex occurred from ~60 to 56 Ma at a time when the crust was significantly partially molten. These structural and temporal relationships suggest a genetic link between mechanical weakening of the crust by partial melting, late-orogenic collapse, and exhumation of high-grade rocks in the hinterland of a thermally mature orogenic belt.


2018 ◽  
Vol 46 (4) ◽  
pp. 305-314 ◽  
Author(s):  
Everett L. Worthington

I examine religious humility, which is one content area of intellectual humility. Intellectual humility is the subtype of humility that involves taking a humble stance in sharing ideas, especially when one is challenged or when an idea is threatening. I position religious humility within the context of general humility, spiritual humility, and relational humility, and thus arrive at several propositions. People who are intensely spiritually humble can hold dogmatic beliefs and believe themselves to be religiously humble, yet be perceived by others of different persuasions as religiously dogmatic and even arrogant. For such people to be truly religiously humble, they must feel that the religious belief is core to their meaning system. This requires discernment of which of the person’s beliefs are truly at the core. But also the religiously humble person must fulfill the definition of general humility, accurately perceiving the strengths and limitations of the self, being teachable to correct weaknesses, presenting oneself modestly, and being positively other-oriented. Humility thus involves (1) beliefs, values, and attitudes and (2) an interpersonal presentational style. Therefore, intellectually humble people must track the positive epistemic status of their beliefs and also must present with convicted civility.


Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1772 ◽  
Author(s):  
Maria de los Angeles Cortes ◽  
Raquel de la Campa ◽  
Maria Luisa Valenzuela ◽  
Carlos Díaz ◽  
Gabino A. Carriedo ◽  
...  

During the last number of years a variety of crystallization-driven self-assembly (CDSA) processes based on semicrystalline block copolymers have been developed to prepare a number of different nanomorphologies in solution (micelles). We herein present a convenient synthetic methodology combining: (i) The anionic polymerization of 2-vinylpyridine initiated by organolithium functionalized phosphane initiators; (ii) the cationic polymerization of iminophosphoranes initiated by –PR2Cl2; and (iii) a macromolecular nucleophilic substitution step, to prepare the novel block copolymers poly(bistrifluoroethoxy phosphazene)-b-poly(2-vinylpyridine) (PTFEP-b-P2VP), having semicrystalline PTFEP core forming blocks. The self-assembly of these materials in mixtures of THF (tetrahydrofuran) and 2-propanol (selective solvent to P2VP), lead to a variety of cylindrical micelles of different lengths depending on the amount of 2-propanol added. We demonstrated that the crystallization of the PTFEP at the core of the micelles is the main factor controlling the self-assembly processes. The presence of pyridinyl moieties at the corona of the micelles was exploited to stabilize gold nanoparticles (AuNPs).


2019 ◽  
Vol 1 (2) ◽  
pp. 207
Author(s):  
Noormawanti, Iswati

The concept of self is an understanding of the attitude of the individual towards himself so that it results in the interaction of two or more people. Self-concept is a factor that communicates with others. The concept of self is the views and attitudes of individuals towards themselves, characteristics and individual and self-motivation. The self-view includes not only individual strengths but also weaknesses and even failures. This self-concept is psychological, social and physical. Self-concept is our views and feelings about ourselves, which include physical, psychological and social aspects. The concept of self is not just a descriptive picture, but also an assessment of ourselves, including what we think and how we feel. Anita Taylor defines self-concept as "all you think and feel about you, the entire complex of beliefs and attitudes you hold abaout yourself '. Human behavior is a product of their interpretation of the world around them through social interaction. Behavior is often a choice as a feasible thing to do based on how it defines the existing situation. The definition they give to other people, situations, objects and even themselves determines their behavior. So it is individuals who are considered active to regulate and determine their own behavior and environment. While the core of the individual is consciousness (consciousness). self-development depends on communication with others, which shape or influence themselves


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Kai Guo ◽  
Senhao Zhang ◽  
Shasha Zhao ◽  
Hongbo Yang

This work takes the production and usage scenarios of the data glove as the research object and studies the method of applying the flexible sensor to the data glove. Many studies are also devoted to exploring the transplantation of flexible sensors to data gloves. However, this type of research still lacks the display of specific application scenarios such as gesture recognition or hand rehabilitation training. A small amount of experimental data and theoretical analysis are difficult to promote the development of flexible sensors and flexible data gloves design schemes. Therefore, this study uses the self-made flexible sensor of the research group as the core sensing unit to produce a flexible data glove to monitor the bending changes of the knuckles and then use it for simple gesture recognition and rehabilitation training.


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