Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation.

Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, and mitochondria have been linked to perturbed cholesterol homeostasis via the study of pathological mutations in the ATAD3 gene cluster. However, whether the cholesterol changes were compensatory or contributory to the disorder was unclear, and the effects on cell membranes and the wider cell were also unknown. Using patient-derived cells, we show that cholesterol perturbation is a conserved feature of pathological ATAD3 variants that is accompanied by an expanded lysosome population containing membrane whorls characteristic of lysosomal storage diseases.

2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart.

2-Deoxy-D-glucose (2DG) has recently received emergency approval for the treatment of COVID-19 in India, after a successful clinical trial. SARS-CoV-2 infection of cultured cells is accompanied by elevated glycolysis and decreased mitochondrial function, whereas 2DG represses glycolysis and stimulates respiration, and restricts viral replication. While 2DG has pleiotropic effects on cell metabolism in cultured cells it is not known which of these manifests in vivo.

2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA.

Pathological variants of human mitochondrial DNA (mtDNA) typically co-exist with wild-type molecules, but the factors driving the selection of each are not understood. Because mitochondrial fitness does not favour the propagation of functional mtDNAs in disease states, we sought to create conditions where it would be advantageous. Glucose and glutamine consumption are increased in mtDNA dysfunction, and so we targeted the use of both in cells carrying the pathogenic m.

Viscoelastic Behaviour of Flexible Thermoplastic Polyurethane Additively Manufactured Parts: Influence of Inner-Structure Design Factors.

Material extrusion based additive manufacturing is used to make three dimensional parts by means of layer-upon-layer deposition. There is a growing variety of polymers that can be processed with material extrusion. Thermoplastic polyurethanes allow manufacturing flexible parts that can be used in soft robotics, wearables and flexible electronics applications.

Probabilistic Assessment of Fracture Toughness of Epoxy Resin EPOLAM 2025 Including the Notch Radii Effect.

Many design scenarios of components made of polymer materials are concerned with notches as representative constructive details. The failure hazard assessment of these components using models based on the assumption of cracked components leads to over-conservative failure estimations. Among the different alternative approaches proposed that are based on the apparent fracture toughness, KcN is considered.

Effect of region-dependent viscoelastic properties on the TMJ articular disc relaxation under prolonged clenching.

The disc of the temporomandibular joint (TMJ) is located between the mandibular condyle and temporal bone, and has an important load-bearing and stress absorbing function. The TMJ disc presents viscoelastic characteristics that are largely dependent on its collagen fibre and proteoglycan composition and organization. The purpose of this study is to investigate the possible effects of region-specific dynamic viscoelastic properties on stress relaxation during prolonged clenching.

Effects of loading direction in prolonged clenching on stress distribution in the temporomandibular joint.

Parafunctional habits, such as bruxism and prolonged clenching, have been associated with dysfunctional hyperactivity of the masticatory muscles, including the lateral pterygoid muscle. The resultant loading to the temporomandibular joint (TMJ) is subject to the degradation of bone, cartilage and disc in the TMJ. In this study, we examined the effect of clenching direction on the stress distribution in the TMJ.

Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified.

Parkinsonism and spastic paraplegia type 7: Expanding the spectrum of mitochondrial Parkinsonism.

Background: Pathogenic variants in the spastic paraplegia type 7 gene cause a complicated hereditary spastic paraplegia phenotype associated with classical features of mitochondrial diseases, including ataxia, progressive external ophthalmoplegia, and deletions of mitochondrial DNA.

Objectives: To better characterize spastic paraplegia type 7 disease with a clinical, genetic, and functional analysis of a Spanish cohort of spastic paraplegia type 7 patients.

Methods: Genetic analysis was performed in patients suspecting hereditary spastic paraplegia and in 1 patient with parkinsonism and Pisa syndrome, through next-generation sequencing, whole-exome sequencing, targeted Sanger sequencing, and multiplex ligation-dependent probe analysis, and blood mitochondrial DNA levels determined by quantitative polymerase chain reaction.

Viscoelastic properties of the central region of porcine temporomandibular joint disc in shear stress-relaxation.

In this study, shear relaxation properties of the porcine temporomandibular joint (TMJ) disc are investigated. Previous studies have shown that, in fatigue failure and damage of cartilage and fibrocartilage, shear loads could be one of the biggest contributors to the failure. The aim of the present study is to develop an evaluation method to study shear properties of the disc and to do a mathematical characterization of it.

Dynamic and stress relaxation properties of the whole porcine temporomandibular joint disc under compression.

In this study, the dynamic and static compressive properties of the whole porcine temporomandibular joint (TMJ) disc were investigated. The aim of the study was to develop a new simple method for the evaluation of joint viscoelasticity, enabling examination of the load-bearing capacity and joint flexibility of the entire disc. For the experiments, a novel testing fixture that reproduces the condylar and fossa surfaces of the TMJ was developed to replicate TMJ disc geometry.

Stress relaxation behaviors of articular cartilages in porcine temporomandibular joint.

In this study, we tested the compressive stress relaxation behaviors of the mandibular condylar and temporal cartilages in the porcine temporomandibular joint (TMJ). The aim was to determine the quantitative and qualitative similarities and differences of compressive stress relaxation behaviors between the two cartilages. Ten porcine TMJs were used; the articular surface was divided into 5 regions: anterior, central, posterior, lateral and medial.

Dynamic compressive properties of articular cartilages in the porcine temporomandibular joint.

The mandibular condylar and temporal cartilages in the temporomandibular joint (TMJ) play an important role as a stress absorber during function. However, relatively little information is available on its viscoelastic properties in dynamic compression, particularly in a physiological range of frequencies. We hypothesized that these properties are region-specific and depend on loading frequency.

The region-dependent dynamic properties of porcine temporomandibular joint disc under unconfined compression.

In this study, the dynamic compressive properties in five different regions of the porcine temporomandibular joint (TMJ) disc are investigated over a wide range of loading frequencies. The aim was, thus far, to evaluate the regional difference and the frequency-related effect of the applied load on these properties. Eleven porcine TMJ discs were used; each disc was divided into 5 regions, anterior, central, posterior, lateral and medial.