The Cortical “Upper Motoneuron” in Health and Disease

Upper motoneurons (UMNs) in motor areas of the cerebral cortex influence spinal and cranial motor mechanisms through the corticospinal tract (CST) and through projections to brainstem motor pathways. The primate corticospinal system has a diverse cortical origin and a wide spectrum of fibre diameters, including large diameter fibres which are unique to humans and other large primates. Direct cortico-motoneuronal (CM) projections from the motor cortex to arm and hand motoneurons are a late evolutionary feature only present in dexterous primates and best developed in humans. CM projections are derived from a more restricted cortical territory (‘new’ M1, area 3a) and arise not only from corticospinal neurons with large, fast axons but also from those with relatively slow-conducting axons. During movement, corticospinal neurons are organised and recruited quite differently from ‘lower’ motoneurons. Accumulating evidence strongly implicates the corticospinal system in the early stages of ALS, with particular involvement of CM projections to distal limb muscles, but also to other muscle groups influenced by the CM system. There are important species differences in the organisation and function of the corticospinal system, and appropriate animal models are needed to understand disorders involving the human corticospinal system.

Download Full-text

Recent advances in our understanding of the primate corticospinal system

F1000Research ◽

10.12688/f1000research.17445.1 ◽

2019 ◽

Vol 8 ◽

pp. 274 ◽

Cited By ~ 14

Author(s):

Roger Lemon

Keyword(s):

Neurological Disease ◽

Corticospinal Tract ◽

New Work ◽

Important Species ◽

Advanced Level ◽

Motor Pathways ◽

Cortical Motor ◽

Motor Network ◽

Species Specific ◽

And Function

The last few years have seen major advances in our understanding of the organisation and function of the corticospinal tract (CST). These have included studies highlighting important species-specific variations in the different functions mediated by the CST. In the primate, the most characteristic feature is direct cortico-motoneuronal (CM) control of muscles, particularly of hand and finger muscles. This system, which is unique to dexterous primates, is probably at its most advanced level in humans. We now know much more about the origin of the CM system within the cortical motor network, and its connectivity within the spinal cord has been quantified. We have learnt much more about how the CM system works in parallel with other spinal circuits receiving input from the CST and how the CST functions alongside other brainstem motor pathways. New work in the mouse has provided fascinating insights into the contribution of the CM system to dexterity. Finally, accumulating evidence for the involvement of CM projections in motor neuron disease has highlighted the importance of advances in basic neuroscience for our understanding and possible treatment of a devastating neurological disease.

Download Full-text

The Laryngeal Epithelium in Reflux

Perspectives on Voice and Voice Disorders ◽

10.1044/vvd21.3.112 ◽

2011 ◽

Vol 21 (3) ◽

pp. 112-117 ◽

Cited By ~ 2

Author(s):

Elizabeth Erickson-Levendoski ◽

Mahalakshmi Sivasankar

Keyword(s):

Laryngopharyngeal Reflux ◽

Critical Role ◽

Structure And Function ◽

Laryngeal Disease ◽

Health And Disease ◽

And Function ◽

The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

Download Full-text

“Because every recipient is also a potential patient” – TV Health Programmes in the FRG and the GDR, from the 1960s to the 1980s

Gesnerus ◽

10.24894/gesn-en.2019.76009 ◽

2019 ◽

Vol 76 (2) ◽

pp. 172-191

Author(s):

Susanne Vollberg

Keyword(s):

Public Awareness ◽

West Germany ◽

Continuous Coverage ◽

Public Consciousness ◽

Television Programme ◽

East German ◽

Health And Disease ◽

Media Systems ◽

The 1960S ◽

And Function

In the television programme of West Germany from the 1960s to the 1980s, health magazines like Gesundheitsmagazin Praxis [Practice Health Magazine] (produced by ZDF)1 or ARD-Ratgeber: Gesundheit [ARD Health Advisor] played an important role in addressing health and disease as topics of public awareness. With their health magazine Visite [Doctor’s rounds], East German television, too relied on continuous coverage and reporting in the field. On the example of above magazines, this paper will examine the history, design and function of health communication in magazine-type formats. Before the background of the changes in media policy experienced over three decades and the different media systems in the then two Germanys, it will discuss the question of whether television was able to move health relevant topics and issues into public consciousness.

Download Full-text

Maturation of the Na,K-ATPase in the Endoplasmic Reticulum in Health and Disease

The Journal of Membrane Biology ◽

10.1007/s00232-021-00184-z ◽

2021 ◽

Author(s):

Vitalii Kryvenko ◽

Olga Vagin ◽

Laura A. Dada ◽

Jacob I. Sznajder ◽

István Vadász

Keyword(s):

Endoplasmic Reticulum ◽

Intracellular Signaling ◽

Loss Of Function ◽

Α Subunit ◽

Rate Limiting Step ◽

Atpase Subunits ◽

A Cell ◽

Health And Disease ◽

And Function ◽

Rate Limiting

Abstract The Na,K-ATPase establishes the electrochemical gradient of cells by driving an active exchange of Na+ and K+ ions while consuming ATP. The minimal functional transporter consists of a catalytic α-subunit and a β-subunit with chaperon activity. The Na,K-ATPase also functions as a cell adhesion molecule and participates in various intracellular signaling pathways. The maturation and trafficking of the Na,K-ATPase include co- and post-translational processing of the enzyme in the endoplasmic reticulum (ER) and the Golgi apparatus and subsequent delivery to the plasma membrane (PM). The ER folding of the enzyme is considered as the rate-limiting step in the membrane delivery of the protein. It has been demonstrated that only assembled Na,K-ATPase α:β-complexes may exit the organelle, whereas unassembled, misfolded or unfolded subunits are retained in the ER and are subsequently degraded. Loss of function of the Na,K-ATPase has been associated with lung, heart, kidney and neurological disorders. Recently, it has been shown that ER dysfunction, in particular, alterations in the homeostasis of the organelle, as well as impaired ER-resident chaperone activity may impede folding of Na,K-ATPase subunits, thus decreasing the abundance and function of the enzyme at the PM. Here, we summarize our current understanding on maturation and subsequent processing of the Na,K-ATPase in the ER under physiological and pathophysiological conditions. Graphic Abstract

Download Full-text

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

International Journal of Molecular Sciences ◽

10.3390/ijms22031416 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1416

Author(s):

Riccardo Castagnoli ◽

Francesca Pala ◽

Marita Bosticardo ◽

Amelia Licari ◽

Ottavia M. Delmonte ◽

...

Keyword(s):

Gut Microbiome ◽

Wide Spectrum ◽

Adaptive Immune System ◽

Clinical Feature ◽

Inborn Errors ◽

Mucosal Permeability ◽

Microbial Dysbiosis ◽

Inborn Errors Of Immunity ◽

Key Aspects ◽

And Function

Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host’s innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.

Download Full-text

Deubiquitylating enzymes in neuronal health and disease

Cell Death and Disease ◽

10.1038/s41419-020-03361-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Fatima Amer-Sarsour ◽

Alina Kordonsky ◽

Yevgeny Berdichevsky ◽

Gali Prag ◽

Avraham Ashkenazi

Keyword(s):

Human Brain ◽

Neurodegenerative Disorders ◽

Structure And Function ◽

Pivotal Role ◽

Protein Homeostasis ◽

Neuronal Function ◽

Health And Disease ◽

And Function

AbstractUbiquitylation and deubiquitylation play a pivotal role in protein homeostasis (proteostasis). Proteostasis shapes the proteome landscape in the human brain and its impairment is linked to neurodevelopmental and neurodegenerative disorders. Here we discuss the emerging roles of deubiquitylating enzymes in neuronal function and survival. We provide an updated perspective on the genetics, physiology, structure, and function of deubiquitylases in neuronal health and disease.

Download Full-text

Plasma proteomics of green turtles (Chelonia mydas) reveals pathway shifts and potential biomarker candidates associated with health and disease

Conservation Physiology ◽

10.1093/conphys/coab018 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

David P Marancik ◽

Justin R Perrault ◽

Lisa M Komoroske ◽

Jamie A Stoll ◽

Kristina N Kelley ◽

...

Keyword(s):

Chelonia Mydas ◽

Sea Turtle ◽

Protein Abundance ◽

Plasma Samples ◽

Important Species ◽

Green Turtles ◽

Rehabilitation Programs ◽

Potential Biomarker ◽

Health And Disease

Abstract Evaluating sea turtle health can be challenging due to an incomplete understanding of pathophysiologic responses in these species. Proteome characterization of clinical plasma samples can provide insights into disease progression and prospective biomarker targets. A TMT-10-plex-LC–MS/MS platform was used to characterize the plasma proteome of five, juvenile, green turtles (Chelonia mydas) and compare qualitative and quantitative protein changes during moribund and recovered states. The 10 plasma samples yielded a total of 670 unique proteins. Using ≥1.2-fold change in protein abundance as a benchmark for physiologic upregulation or downregulation, 233 (34.8%) were differentially regulated in at least one turtle between moribund and recovered states. Forty-six proteins (6.9%) were differentially regulated in all five turtles with two proteins (0.3%) demonstrating a statistically significant change. A principle component analysis showed protein abundance loosely clustered between moribund samples or recovered samples and for turtles that presented with trauma (n = 3) or as intestinal floaters (n = 2). Gene Ontology terms demonstrated that moribund samples were represented by a higher number of proteins associated with blood coagulation, adaptive immune responses and acute phase response, while recovered turtle samples included a relatively higher number of proteins associated with metabolic processes and response to nutrients. Abundance levels of 48 proteins (7.2%) in moribund samples significantly correlated with total protein, albumin and/or globulin levels quantified by biochemical analysis. Differentially regulated proteins identified with immunologic and physiologic functions are discussed for their possible role in the green turtle pathophysiologic response and for their potential use as diagnostic biomarkers. These findings enhance our ability to interpret sea turtle health and further progress conservation, research and rehabilitation programs for these ecologically important species.

Download Full-text

Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases

Nutrients ◽

10.3390/nu13030850 ◽

2021 ◽

Vol 13 (3) ◽

pp. 850

Author(s):

María Ángeles Martín ◽

Sonia Ramos

Keyword(s):

Immune System ◽

Fruits And Vegetables ◽

Metabolic Diseases ◽

Nuclear Factor Κb ◽

Low Grade ◽

Beneficial Effects ◽

Health And Disease ◽

Immunological Reactions ◽

And Function ◽

Positive Properties

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.

Download Full-text