Search results for "SKELETAL"

FGFR a promising druggable target in cancer: Molecular biology and new drugs.

2017

Abstract: Introduction: The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. Areas Covered: This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Expert opinion: Most of the TKR share …

Skeletal Dysplasia Mutations Effect on Human Filamins’ Structure and Mechanosensing

2016

AbstractCells’ ability to sense mechanical cues in their environment is crucial for fundamental cellular processes, leading defects in mechanosensing to be linked to many diseases. The actin cross-linking protein Filamin has an important role in the conversion of mechanical forces into biochemical signals. Here, we reveal how mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. Employing X-ray crystallography, the structure of these domains was first solved for the human Filamin B. The interaction seen between domains 16 and 17 is broken by shear force as revealed by steered mo…

Special Issue "Human performance and redox signaling in health and disease".

2016

Deciphering the functional role of spatial and temporal muscle synergies in whole-body movements

2018

AbstractVoluntary movement is hypothesized to rely on a limited number of muscle synergies, the recruitment of which translates task goals into effective muscle activity. In this study, we investigated how to analytically characterize the functional role of different types of muscle synergies in task performance. To this end, we recorded a comprehensive dataset of muscle activity during a variety of whole-body pointing movements. We decomposed the electromyographic (EMG) signals using a space-by-time modularity model which encompasses the main types of synergies. We then used a task decoding and information theoretic analysis to probe the role of each synergy by mapping it to specific task …

Polysialic Acid Acute Depletion Induces Structural Plasticity in Interneurons and Impairs the Excitation/Inhibition Balance in Medial Prefrontal Cort…

2016

The structure and function of the medial prefrontal cortex (mPFC) is affected in several neuropsychiatric disorders, including schizophrenia and major depression. Recent studies suggest that imbalances between excitatory and inhibitory activity (E/I) may be responsible for this cortical dysfunction and, therefore, may underlie the core symptoms of these diseases. This E/I imbalance seems to be correlated with alterations in the plasticity of interneurons but there is still scarce information on the mechanisms that may link these phenomena. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is a good candidate, because it modulates the neuronal plasticity of interneurons…

FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability

2021

Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and pr…

Biology of frailty: Modulation of ageing genes and its importance to prevent age-associated loss of function

2016

Frailty is associated with loss of functional reserve as well as with the prediction of adverse events in the old population. The traditional criteria of frailty are based on five physical determinations described in the Cardiovascular Health Study. We propose that biological and genetic markers of frailty should be used to increase the predictive capacity of the established clinical indeces. In recent times, research for biological markers of frailty has gained impetus. Finding a biological markers with diagnostic and prognostic capacity would be a major milestone to identify frailty risk, and also pre-frailty status. In the first section of the manuscript, we review the available biomarke…

Sarcopenia, frailty and their prevention by exercise.

2019

Sarcopenia is a major component of the frailty syndrome, both being considered as strong predictors of morbidity, disability, and death in older people. In this review, we explore the definitions of sarcopenia and frailty and summarize the current knowledge on their relationship with oxidative stress and the possible therapeutic interventions to prevent or treat them, including exercise-based interventions and multimodal strategies. We highlight the relevance of the impairment of the nervous system and of the anabolic response (protein synthesis) in muscle aging leading to frailty and sarcopenia. We also discuss the importance of malnutrition and physical inactivity in these geriatric syndr…

Cardiac regenerative capacity is age- and disease-dependent in childhood heart disease

2018

Objective We sought to define the intrinsic stem cell capacity in pediatric heart lesions, and the effects of diagnosis and of age, in order to inform evidence-based use of potential autologous stem cell sources for regenerative medicine therapy. Methods Ventricular explants derived from patients with hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TF), dilated cardiomyopathy (DCM) and ventricular septal defect (VSD) were analyzed following standard in vitro culture conditions, which yielded cardiospheres (C-spheres), indicative of endogenous stem cell capacity. C-sphere counts generated per 5 mm3 tissue explant and the presence of cardiac progenitor cells were correlated to pa…

Can the transverse foramen/vertebral artery ratio of double transverse foramen subjects be a risk for vertebrobasilar transient ischemic attacks?

2018

The C6 is the cervical vertebra into which the vertebral artery enters the passage of the transverse foramen and it is the vertebra most affected by double transverse foramina. There is currently little information about the relation between the vertebral artery and the double transverse foramen in C6. We aimed to test whether subjects with a double transverse foramen in C6 have a reduced transverse foramen/vertebral artery ratio when compared with normal anatomy subjects who possess a single transverse foramen which may be a risk for transient vertebral artery stenosis. We measured the area of the transverse foramen and the vertebral artery in 27 double transverse and 56 normal anatomy sub…