scholarly journals Neurofilaments: neurobiological foundations for biomarker applications

Brain ◽  
2020 ◽  
Vol 143 (7) ◽  
pp. 1975-1998 ◽  
Author(s):  
Arie R Gafson ◽  
Nicolas R Barthélemy ◽  
Pascale Bomont ◽  
Roxana O Carare ◽  
Heather D Durham ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intermediate Filaments ◽  
Neuronal Injury ◽  
Structure And Function ◽  
Current Understanding ◽  
Human Diseases ◽  
Neurofilament Proteins ◽  
New Methods ◽  
And Function ◽  
Kinetics Of

Abstract Interest in neurofilaments has risen sharply in recent years with recognition of their potential as biomarkers of brain injury or neurodegeneration in CSF and blood. This is in the context of a growing appreciation for the complexity of the neurobiology of neurofilaments, new recognition of specialized roles for neurofilaments in synapses and a developing understanding of mechanisms responsible for their turnover. Here we will review the neurobiology of neurofilament proteins, describing current understanding of their structure and function, including recently discovered evidence for their roles in synapses. We will explore emerging understanding of the mechanisms of neurofilament degradation and clearance and review new methods for future elucidation of the kinetics of their turnover in humans. Primary roles of neurofilaments in the pathogenesis of human diseases will be described. With this background, we then will review critically evidence supporting use of neurofilament concentration measures as biomarkers of neuronal injury or degeneration. Finally, we will reflect on major challenges for studies of the neurobiology of intermediate filaments with specific attention to identifying what needs to be learned for more precise use and confident interpretation of neurofilament measures as biomarkers of neurodegeneration.

scholarly journals Discovery of keratin function and role in genetic diseases: the year that 1991 was

2016 ◽  
Vol 27 (18) ◽  
pp. 2807-2810 ◽  
Author(s):  
Pierre A. Coulombe
Keyword(s):  
Intermediate Filaments ◽  
Cell Biology ◽  
Essential Role ◽  
Genetic Diseases ◽  
Structure And Function ◽  
Mechanical Support ◽  
25Th Anniversary ◽  
Keratin Filaments ◽  
And Function ◽  
Keratin Intermediate Filaments

In 1991, a set of transgenic mouse studies took the fields of cell biology and dermatology by storm in providing the first credible evidence that keratin intermediate filaments play a unique and essential role in the structural and mechanical support in keratinocytes of the epidermis. Moreover, these studies intimated that mutations altering the primary structure and function of keratin filaments underlie genetic diseases typified by cellular fragility. This Retrospective on how these studies came to be is offered as a means to highlight the 25th anniversary of these discoveries.

Structure and Function of the Plant Alternative Oxidase: Its Putative Role in the Oxygen Defence Mechanism

1997 ◽  
Vol 17 (3) ◽  
pp. 319-333 ◽  
Author(s):  
Anneke M. Wagner ◽  
Anthony L. Moore
Keyword(s):  
Oxidative Stress ◽  
Alternative Oxidase ◽  
Structure And Function ◽  
Current Understanding ◽  
Defence Mechanism ◽  
Putative Role ◽  
And Function

Current understanding of the structure and function of the plant alternative oxidase is reviewed. In particular, the role of the oxidase in the protection of tissues against oxidative stress is developed.

Endogenous ion channel complexes: the NMDA receptor

2011 ◽  
Vol 39 (3) ◽  
pp. 707-718 ◽  
Author(s):  
René A.W. Frank
Keyword(s):  
Nmda Receptor ◽  
Ion Channel ◽  
Present Article ◽  
Neuronal Excitability ◽  
Structure And Function ◽  
Current Understanding ◽  
Ionotropic Receptors ◽  
Receptor Complexes ◽  
Aspartate Receptor ◽  
And Function

Ionotropic receptors, including the NMDAR (N-methyl-D-aspartate receptor) mediate fast neurotransmission, neurodevelopment, neuronal excitability and learning. In the present article, the structure and function of the NMDAR is reviewed with the aim to condense our current understanding and highlight frontiers where important questions regarding the biology of this receptor remain unanswered. In the second part of the present review, new biochemical and genetic approaches for the investigation of ion channel receptor complexes will be discussed.

Comparison of the structure and function of ribulosebisphosphate carboxylase–oxygenase from a cold-hardy and nonhardy potato species

1981 ◽  
Vol 59 (4) ◽  
pp. 280-289 ◽  
Author(s):  
Norman P. A. Huner ◽  
Jiwan P. Palta ◽  
Paul H. Li ◽  
John V. Carter
Keyword(s):  
Large Subunit ◽  
Structure And Function ◽  
Sulfhydryl Groups ◽  
Relative Mass ◽  
Nitrobenzoic Acid ◽  
Significant Difference ◽  
Ribulosebisphosphate Carboxylase ◽  
Cold Hardy ◽  
And Function ◽  
Kinetics Of

A comparison of ribulosebisphosphate carboxylase–oxygenase from the leaves of the non-acclimated, cold-hardy species, Solanum commersonii, and the nonacclimated, nonhardy species, Solanum tuberosum showed that this enzyme from the two species differed in structure and function. The results of sulfhydryl group titration with 5,5′-dithiobis(2-nitrobenzoic acid) indicated that the kinetics of titration and the number of accessible sulfhydryl groups in the native enzymes were different. After 30 min, the enzyme from the hardy species had 1.7 times fewer sulfhydryl groups titrated than that from the nonhardy species. In the presence of 1% (w/v) sodium dodecyl sulfate, the total number of sulfhydryl groups titratable with 5,5′-dithiobis-(2-nitrobenzoic acid) was the same for both species. However, this denaturant had a differential effect on the kinetics of titration with 5,5′-dithiobis(2-nitrobenzoic acid). Both enzymes had a native molecular weight of about 550 000. The quaternary structures of the two enzymes were similar with the presence of large and small subunits of 54 000 and 14 000, respectively. However, there was more polypeptide of 108 000 – 110 000 present in preparations of the enzyme from S. tuberosum than from S. commersonii. This polypeptide is an apparent dimer of the large subunit on a relative mass basis. The large subunit of the enzyme from S. tuberosum was more sensitive to the absence of reducing agent and was more sensitive to freezing and thawing than the large subunit of the enzyme from S. commersonii. Catalytic properties of both enzymes at 5 and 25 °C indicated no significant difference in the [Formula: see text] at either temperature. However, the Vmax at 5 °C for the enzyme from S. commersonii was 35% higher than that of the enzyme from S. tuberosum. In contrast, the Vmax at 25 °C for the enzyme of the hardy species was 250% lower than that of the enzyme from the nonhardy species.

scholarly journals Current understanding of the structure and function of family B GPCRs to design novel drugs

HORMONES ◽  
2018 ◽  
Vol 17 (1) ◽  
pp. 45-59 ◽  
Author(s):  
Vlasios Karageorgos ◽  
Maria Venihaki ◽  
Stelios Sakellaris ◽  
Michail Pardalos ◽  
George Kontakis ◽  
...  
Keyword(s):  
Structure And Function ◽  
Current Understanding ◽  
Novel Drugs ◽  
And Function

Neuroimaging of Psychotic Disorders

2013 ◽  
pp. 256-268
Author(s):  
Stephan Heckers ◽  
Neil Woodward ◽  
Dost ÖNgür
Keyword(s):  
Schizoaffective Disorder ◽  
Research Methodology ◽  
Brain Structure ◽  
Psychotic Disorders ◽  
Structure And Function ◽  
Current Understanding ◽  
Brain Images ◽  
Brain Structure And Function ◽  
Meta Analyses ◽  
And Function

Neuroimaging studies of brain structure and function have significantly advanced our understanding of psychotic disorders by capturing the pathology with brain images. This chapter provides an overview of the neuroimaging studies of psychotic disorders (mainly schizophrenia and schizoaffective disorder). This will focus on meta-analyses and comprehensive reviews, but will include some seminal studies that have shaped the current understanding of psychotic disorders. The ability to study brain structure and function repeatedly and to correlate it with cognitive and clinical outcomes are unique strengths of neuroimaging studies and will ensure a prominent position of this research methodology in the study of psychotic disorders.

scholarly journals Kids’ Outcomes And Long-term Abilities (KOALA): protocol for a prospective, longitudinal cohort study of mild traumatic brain injury in children 6 months to 6 years of age

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e040603 ◽  
Author(s):  
Miriam H Beauchamp ◽  
Fanny Dégeilh ◽  
Keith Yeates ◽  
Isabelle Gagnon ◽  
Ken Tang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Traumatic Brain Injury ◽  
Cohort Study ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Structure And Function ◽  
Brain Structure And Function ◽  
And Function

IntroductionMild traumatic brain injury (mTBI) is highly prevalent, especially in children under 6 years. However, little research focuses on the consequences of mTBI early in development. The objective of the Kids’ Outcomes And Long-term Abilities (KOALA) study is to document the impact of early mTBI on children’s motor, cognitive, social and behavioural functioning, as well as on quality of life, stress, sleep and brain integrity.Methods and analysesKOALA is a prospective, multicentre, longitudinal cohort study of children aged 6 months to 6 years at the time of injury/recruitment. Children who sustain mTBI (n=150) or an orthopaedic injury (n=75) will be recruited from three paediatric emergency departments (PEDs), and compared with typically developing children (community controls, n=75). A comprehensive battery of prognostic and outcome measures will be collected in the PED, at 10 days, 1, 3 and 12 months postinjury. Biological measures, including measures of brain structure and function (magnetic resonance imaging, MRI), stress (hair cortisol), sleep (actigraphy) and genetics (saliva), will complement direct testing of function using developmental and neuropsychological measures and parent questionnaires. Group comparisons and predictive models will test the a priori hypotheses that, compared with children from the community or with orthopaedic injuries, children with mTBI will (1) display more postconcussive symptoms and exhibit poorer motor, cognitive, social and behavioural functioning; (2) show evidence of altered brain structure and function, poorer sleep and higher levels of stress hormones. A combination of child, injury, socioenvironmental and psychobiological factors are expected to predict behaviour and quality of life at 1, 3 and 12 months postinjury.Ethics and disseminationThe KOALA study is approved by the Sainte-Justine University Hospital, McGill University Health Centre and University of Calgary Conjoint Health Research Ethics Boards. Parents of participants will provide written consent. Dissemination will occur through peer-reviewed journals and an integrated knowledge translation plan.

scholarly journals The SARS-CoV-2 spike reversibly samples an open-trimer conformation exposing novel epitopes

2021 ◽  
Author(s):  
Shawn M Costello ◽  
Sophie R Shoemaker ◽  
Helen T Hobbs ◽  
Annalee W Nguyen ◽  
Ching-Lin Hsieh ◽  
...  
Keyword(s):  
Structure And Function ◽  
Clinical Diagnostics ◽  
Hydrogen Deuterium Exchange ◽  
Exchange Mass Spectrometry ◽  
Alternative Conformation ◽  
Hydrogen Deuterium ◽  
Deuterium Exchange Mass Spectrometry ◽  
Binding Antibody ◽  
And Function ◽  
Kinetics Of

Current COVID-19 vaccines and many clinical diagnostics are based on the structure and function of the SARS-CoV-2 spike ectodomain. Using hydrogen deuterium exchange mass spectrometry, we have uncovered that, in addition to the prefusion structure determined by cryo-EM, this protein adopts an alternative conformation that interconverts slowly with the canonical prefusion structure. This new conformation-an open trimer-contains easily accessible RBDs. It exposes the conserved trimer interface buried in the prefusion conformation, thus exposing potential epitopes for pan-coronavirus antibody and ligand recognition. The population of this state and kinetics of interconversion are modulated by temperature, receptor binding, antibody binding, and sequence variants observed in the natural population. Knowledge of the structure and populations of this conformation will help improve existing diagnostics, therapeutics, and vaccines.

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