scholarly journals Recent advances in our understanding of the primate corticospinal system

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 274 ◽  
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.

scholarly journals The Cortical “Upper Motoneuron” in Health and Disease

2021 ◽  
Vol 11 (5) ◽  
pp. 619
Author(s):  
Roger N. Lemon
Keyword(s):  
Species Differences ◽  
Wide Spectrum ◽  
Large Diameter ◽  
Important Species ◽  
Motor Pathways ◽  
Corticospinal System ◽  
Area 3A ◽  
Health And Disease ◽  
Muscle Groups ◽  
And Function

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.

scholarly journals Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiya Börsch ◽  
Daniel J. Ham ◽  
Nitish Mittal ◽  
Lionel A. Tintignac ◽  
Eugenia Migliavacca ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Inflammatory Responses ◽  
Molecular Data ◽  
Model Organisms ◽  
Sequencing Data ◽  
Phenotypic Analysis ◽  
Age Related ◽  
Analogous Data ◽  
Species Specific ◽  
And Function

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.

scholarly journals Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Neeraja Punde ◽  
Jennifer Kooken ◽  
Dagmar Leary ◽  
Patricia M. Legler ◽  
Evelina Angov
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Codon Usage ◽  
Dna Sequences ◽  
Structural Integrity ◽  
Host Cells ◽  
Loss Of Function ◽  
Species Specific ◽  
And Function ◽  
The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

The Structure and Function of the Developing Corticospinal Tract

1996 ◽  
pp. 125-145 ◽  
Author(s):  
J. Armand ◽  
E. Olivier ◽  
R.N. Lemon ◽  
S.A. Edgley
Keyword(s):  
Corticospinal Tract ◽  
Structure And Function ◽  
And Function

Introduction and approach to the patient with neurological disease

2010 ◽  
pp. 4743-4745
Author(s):  
Alastair Compston
Keyword(s):  
Neurological Disease ◽  
Relevant Information ◽  
Structure And Function ◽  
Clinical Neurology ◽  
Health And Disease ◽  
Laboratory Investigations ◽  
And Function

Clinical neurology uses conversation, detailed questioning and discussion, observation, structured examination, and selective investigation to formulate problems into an anatomical and pathological framework. The competent neurologist senses and probes relevant components of the history, reliably elicits the physical signs, knows which investigations are necessary and relevant, appreciates the most likely underlying diagnosis and mechanism of disease, and communicates relevant information to the patient accurately, intelligibly, and sensitively. This system has evolved over several centuries, during which much knowledge has accumulated on structure and function in health and disease, the reliability of physical signs and laboratory investigations, and the nosology of disease....

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