scholarly journals pS421 huntingtin modulates mitochondrial phenotypes and confers neuroprotection in an HD hiPSC model

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Xiaohong Xu ◽  
Bryan Ng ◽  
Bernice Sim ◽  
Carola I. Radulescu ◽  
Nur Amirah Binte Mohammad Yusof ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Neurodegenerative Disorder ◽  
Protective Role ◽  
Neural Cells ◽  
Rodent Models ◽  
Form And Function ◽  
And Function ◽  
The Relationship ◽  
Genetic Context

Abstract Huntington disease (HD) is a hereditary neurodegenerative disorder caused by mutant huntingtin (mHTT). Phosphorylation at serine-421 (pS421) of mHTT has been shown to be neuroprotective in cellular and rodent models. However, the genetic context of these models differs from that of HD patients. Here we employed human pluripotent stem cells (hiPSCs), which express endogenous full-length mHTT. Using genome editing, we generated isogenic hiPSC lines in which the S421 site in mHTT has been mutated into a phospho-mimetic aspartic acid (S421D) or phospho-resistant alanine (S421A). We observed that S421D, rather than S421A, confers neuroprotection in hiPSC-derived neural cells. Although we observed no effect of S421D on mHTT clearance or axonal transport, two aspects previously reported to be impacted by phosphorylation of mHTT at S421, our analysis revealed modulation of several aspects of mitochondrial form and function. These include mitochondrial surface area, volume, and counts, as well as improved mitochondrial membrane potential and oxidative phosphorylation. Our study validates the protective role of pS421 on mHTT and highlights a facet of the relationship between mHTT and mitochondrial changes in the context of human physiology with potential relevance to the pathogenesis of HD.

1. Everything has structure

2014 ◽  
Author(s):  
David Blockley
Keyword(s):  
Decision Making ◽  
Structural Engineering ◽  
Fitness For Purpose ◽  
Form And Function ◽  
Environmental Criteria ◽  
Flow Through ◽  
And Function ◽  
Relationship Of ◽  
The Relationship

‘Everything has structure’ considers the fundamental nature and role of structure and the relationship of structural engineering with other engineering disciplines and with architecture. Decision making is driven by the purpose of a man-made structure and how ‘fitness for purpose’ is realised. There is a need to understand how forces flow through a structure in order to ensure it meets its primary purpose of being strong and safe whilst at the same time meeting many other needs such as affordability, aesthetic, and regulatory and environmental criteria. The best structures are a harmony of architecture and engineering—where form and function are one and the flow of forces is logical.

The Left Needs Rhythm

2019 ◽  
pp. 181-218
Author(s):  
Sarah Ehlers
Keyword(s):  
Political Community ◽  
Community Formation ◽  
Popular Front ◽  
Jewish American ◽  
Form And Function ◽  
Lorine Niedecker ◽  
Historical Relationship ◽  
And Function ◽  
The Relationship

This chapter considers the role of the archive in left literary studies through a recovery of Jewish-American communist poet Martha Millet. Specifically, it uses Millet’s work to trace a history and theory of poetic rhythm that rethinks the relationship between modernist poetic forms and left politics. The chapter’s first section uses Millet’s involvement with the children’s magazine The New Pioneer to unpack the historical relationship between traditional forms and political community formation. The generic histories enacted by communist children’s poems provide a foundation for considering how rhythm was evoked in Popular Front and antifascist poetic discourses. The second section argues that during the Popular Front diverse traditional genres were collapsed into an ideal rhythmic poem, where rhythm described both form and function. The third section focuses on Millet’s contributions to Seven Poets in Search of an Answer (1944) to demonstrate how rhythm was redefined in antifascist discourses. Throughout, the chapter suggests how Millet’s poetry might be read in relation to poets such as Carl Sandburg, Lorine Niedecker, and Kenneth Fearing. A coda returns to Millet’s Cold War criticism in order to ask what is at stake in her critical erasure and her critical recovery.

scholarly journals The People and the Poster: Theorizing the Soviet Viewer, 1920–1931

Slavic Review ◽  
2019 ◽  
Vol 78 (3) ◽  
pp. 717-737
Author(s):  
Mollie Arbuthnot
Keyword(s):  
Political Art ◽  
Political Messages ◽  
Form And Function ◽  
Modern Subject ◽  
The People ◽  
Intellectual Context ◽  
The Individual ◽  
And Function ◽  
The Relationship

The relationship between political posters and their intended viewers was the focus of numerous texts in the 1920s; this article analyzes the ways in which Soviet theorists sought to understand this relationship. They operated in an intellectual context that tried to conceive the modern subject as an active consumer and co-creator, rather than a passive audience. Their study of the contexts of viewing, of display practices and of the role of the viewer as an active participant in the creation of meaning, caused concern about the risk of misunderstandings and led to calls for images to address specific audiences with greater clarity. Many imagined that audiences and producers of images were in dialogue with one another, negotiating over the content, form, and function of political art. The image would thus mediate the relationship between individual and state, integrating political messages into everyday life, and aiming to integrate the individual into the process and practice of propaganda.

Scanning tunneling microscopy (STM) of DNA and RNA

1989 ◽  
Vol 47 ◽  
pp. 34-35
Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans
Keyword(s):  
Molecular Structures ◽  
Inorganic Materials ◽  
Resolving Power ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Form And Function ◽  
Dna And Rna ◽  
Calf Thymus ◽  
And Function ◽  
The Relationship

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).

Parenting Behaviors and Anxiety in Young Adults

2015 ◽  
Vol 36 (3) ◽  
pp. 170-176 ◽  
Author(s):  
Erin N. Stevens ◽  
Joseph R. Bardeen ◽  
Kyle W. Murdock
Keyword(s):  
Effortful Control ◽  
Parenting Behaviors ◽  
Protective Role ◽  
Anxiety Symptoms ◽  
Interactive Effects ◽  
Parental Overprotection ◽  
High Control ◽  
Development Of Anxiety ◽  
The Relationship

Parenting behaviors – specifically behaviors characterized by high control, intrusiveness, rejection, and overprotection – and effortful control have each been implicated in the development of anxiety pathology. However, little research has examined the protective role of effortful control in the relation between parenting and anxiety symptoms, specifically among adults. Thus, we sought to explore the unique and interactive effects of parenting and effortful control on anxiety among adults (N = 162). Results suggest that effortful control uniquely contributes to anxiety symptoms above and beyond that of any parenting behavior. Furthermore, effortful control acted as a moderator of the relationship between parental overprotection and anxiety, such that overprotection is associated with anxiety only in individuals with lower levels of effortful control. Implications for potential prevention and intervention efforts which specifically target effortful control are discussed. These findings underscore the importance of considering individual differences in self-regulatory abilities when examining associations between putative early-life risk factors, such as parenting, and anxiety symptoms.

scholarly journals The Protective Role of Brain CYP2J in Parkinson’s Disease Models

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yueran Li ◽  
Jinhua Wu ◽  
Xuming Yu ◽  
Shufang Na ◽  
Ke Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Regions ◽  
Protective Role ◽  
Neural Cells ◽  
Endogenous Substrates ◽  
6 Hydroxydopamine ◽  
Myd88 Signaling ◽  
Lps Treatment

CYP2J proteins are present in the neural cells of human and rodent brain regions. The aim of this study was to investigate the role of brain CYP2J in Parkinson’s disease. Rats received right unilateral injection with lipopolysaccharide (LPS) or 6-hydroxydopamine (6-OHDA) in the substantia nigra following transfection with or without the CYP2J3 expression vector. Compared with LPS-treated rats, CYP2J3 transfection significantly decreased apomorphine-induced rotation by 57.3% at day 12 and 47.0% at day 21 after LPS treatment; moreover, CYP2J3 transfection attenuated the accumulation of α-synuclein. Compared with the 6-OHDA group, the number of rotations by rats transfected with CYP2J3 decreased by 59.6% at day 12 and 43.5% at day 21 after 6-OHDA treatment. The loss of dopaminergic neurons and the inhibition of the antioxidative system induced by LPS or 6-OHDA were attenuated following CYP2J3 transfection. The TLR4-MyD88 signaling pathway was involved in the downregulation of brain CYP2J induced by LPS, and CYP2J transfection upregulated the expression of Nrf2 via the inhibition of miR-340 in U251 cells. The data suggest that increased levels of CYP2J in the brain can delay the pathological progression of PD initiated by inflammation or neurotoxins. The alteration of the metabolism of the endogenous substrates (e.g., AA) could affect the risk of neurodegenerative disease.

scholarly journals Plered Ceramic Production by Innovation in Products

2021 ◽  
Vol 8 (9) ◽  
pp. 120
Author(s):  
Yuliarni Yuliarni ◽  
Rustopo Rustopo ◽  
Guntur Guntur ◽  
Timbul Raharjo
Keyword(s):  
Product Innovation ◽  
Ceramic Production ◽  
Innovation Development ◽  
Form And Function ◽  
Type Form ◽  
Production Techniques ◽  
Product And Process ◽  
And Function ◽  
Process Product

This article explores the production, in particular innovation, of Plered ceramics. Innovation development seeks to recognize innovations and improvements, as well as the role of institutions in the ceramic industry at Plered. The analysis approach used is qualitative, through observation, interviews, literature review data sources are collected.The results showed that the development of Plered ceramics was carried out in terms of product and process. Product innovation occurs in aspects of type, form and function, while process innovation occurs in aspects of ideas, materials and production techniques. The roles of government, academics, entrepreneurs and consumers who work together are very supportive of the development of Plered ceramics.

An exploration of adolescent nonsuicidal self-injury and religious coping

2014 ◽  
Vol 26 (3) ◽  
pp. 345-349 ◽  
Author(s):  
Nicholas J. Westers ◽  
Mark Rehfuss ◽  
Lynn Olson ◽  
Constance M. Wiemann
Keyword(s):  
Religious Coping ◽  
Self Injury ◽  
Negative Religious Coping ◽  
Religious Constructs ◽  
And Function ◽  
Role Of Religion ◽  
The Relationship ◽  
Pearson Correlations ◽  
Nonsuicidal Self Injury

Abstract Many adolescents who engage in nonsuicidal self-injury (NSSI) self-identify as religious, but the role of religion in their NSSI is not known. This exploratory study examined the relationship between religious coping and religiousness among adolescents who self-injure and the function of their NSSI. Thirty adolescents aged 12–19 years who had engaged in NSSI participated in an interview and completed questionnaires. Multiple regressions were used to examine the relationship between religious coping and NSSI, and Pearson correlations were used to assess the relationship between religiousness and function of NSSI. Greater use of positive religious coping was associated with lower likelihood of engaging in NSSI to rid oneself of unwanted emotions, whereas greater use of negative religious coping was associated with greater likelihood of engaging in NSSI for this reason as well as to avoid punishment or unwanted responsibility. Higher religiousness was associated with greater use of NSSI to communicate with or gain attention from others, whereas lower religiousness was associated with greater use of NSSI to relieve unwanted emotions. Having a greater understanding of how religious constructs are related to the various functions served by NSSI may inform treatment of this population, particularly among religious youth who self-injure.

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