The role of cGMP signalling in auditory processing in health and disease

Abstract Precise auditory perception at a subcortical level (neural representation and encoding of sound) has been suggested as a form of implicit L2 aptitude in naturalistic settings. Emerging evidence suggests that such implicit aptitude explains some variance in L2 speech perception and production among adult learners with different first language backgrounds and immersion experience. By examining 46 Chinese learners of English, the current study longitudinally investigated the extent to which explicit and implicit auditory processing ability could predict L2 segmental and prosody acquisition over a 5-month early immersion. According to the results, participants’ L2 gains were associated with more explicit and integrative auditory processing ability (remembering and reproducing music sequences), while the role of implicit, preconscious perception appeared to be negligible at the initial stage of postpubertal L2 speech learning.

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Chromosome Instability, Aging and Brain Diseases

Cells ◽

10.3390/cells10051256 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1256

Author(s):

Ivan Y. Iourov ◽

Yuri B. Yurov ◽

Svetlana G. Vorsanova ◽

Sergei I. Kutsev

Keyword(s):

Brain Aging ◽

Chromosome Instability ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Accelerated Aging ◽

Brain Diseases ◽

Aging Brain ◽

Ontogenetic Changes ◽

Health And Disease

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.

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The Role of Cell Metabolism in Innate Immune Memory

Journal of Innate Immunity ◽

10.1159/000512280 ◽

2020 ◽

pp. 1-9

Author(s):

Anaisa Valido Ferreira ◽

Jorge Domiguéz-Andrés ◽

Mihai Gheorghe Netea

Keyword(s):

Metabolic Pathways ◽

Tricarboxylic Acid Cycle ◽

Cell Metabolism ◽

Innate Immune ◽

Immune Memory ◽

Functional Changes ◽

Trained Immunity ◽

Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

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Role of Insulin in Health and Disease: An Update

International Journal of Molecular Sciences ◽

10.3390/ijms22126403 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6403

Author(s):

Md Saidur Rahman ◽

Khandkar Shaharina Hossain ◽

Sharnali Das ◽

Sushmita Kundu ◽

Elikanah Olusayo Adegoke ◽

...

Keyword(s):

Insulin Signaling ◽

Basic Research ◽

Future Research ◽

Protective Effects ◽

Glucose Levels ◽

Physiological Processes ◽

Blood Glucose Levels ◽

Wide Range ◽

Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

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A modular tool to query and inducibly disrupt biomolecular condensates

Nature Communications ◽

10.1038/s41467-021-22096-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Carmen N. Hernández-Candia ◽

Sarah Pearce ◽

Chandra L. Tucker

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Cellular Function ◽

Biological Role ◽

Cellular Biology ◽

Condensate Formation ◽

Health And Disease ◽

Lateral Sclerosis

AbstractDynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.

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Role of PRAS40 in Akt and mTOR signaling in health and disease

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00660.2011 ◽

2012 ◽

Vol 302 (12) ◽

pp. E1453-E1460 ◽

Cited By ~ 92

Author(s):

Claudia Wiza ◽

Emmani B. M. Nascimento ◽

D. Margriet Ouwens

Keyword(s):

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Cellular Growth ◽

S6 Kinase ◽

Binding Partners ◽

Health And Disease ◽

Mtor Complex 1 ◽

Mtor Activity

The proline-rich Akt substrate of 40 kDa (PRAS40) acts at the intersection of the Akt- and mammalian target of rapamycin (mTOR)-mediated signaling pathways. The protein kinase mTOR is the catalytic subunit of two distinct signaling complexes, mTOR complex 1 (mTORC1) and mTORC2, that link energy and nutrients to the regulation of cellular growth and energy metabolism. Activation of mTOR in response to nutrients and growth factors results in the phosphorylation of numerous substrates, including the phosphorylations of S6 kinase by mTORC1 and Akt by mTORC2. Alterations in Akt and mTOR activity have been linked to the progression of multiple diseases such as cancer and type 2 diabetes. Although PRAS40 was first reported as substrate for Akt, investigations toward mTOR-binding partners subsequently identified PRAS40 as both component and substrate of mTORC1. Phosphorylation of PRAS40 by Akt and by mTORC1 itself results in dissociation of PRAS40 from mTORC1 and may relieve an inhibitory constraint on mTORC1 activity. Adding to the complexity is that gene silencing studies indicate that PRAS40 is also necessary for the activity of the mTORC1 complex. This review summarizes the regulation and potential function(s) of PRAS40 in the complex Akt- and mTOR-signaling network in health and disease.

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