ITPR3-associated neuropathy: Report of a further family with adult onset intermediate Charcot-Marie-Tooth disease.

Background And Purpose: ITPR3 encodes type 3 inositol-tri-phosphate receptor (IPR3), a protein expressed in Schwann cells, predominantly in the paranodal region, and involved in the regulation of Ca release from the endoplasmic reticulum. Dominant variants in ITPR3 have recently been recognized as a rare cause of intermediate Charcot-Marie-Tooth disease (CMT).

Methods: We collected the clinical data of a family with autosomal dominant neuropathy whose proband was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) for many years.

Insights into phenotypic variability caused by GARS1 pathogenic variants.

Background And Purpose: Pathogenic variants of the glycyl-tRNA synthetase 1 (GARS1) gene have been described as a cause of Charcot-Marie-Tooth disease type 2D, motor axonal neuropathy with upper limb predominance (distal hereditary motor neuropathy [dHMN] type V), and infantile spinal muscular atrophy.

Methods: This cross-sectional, retrospective, observational study was carried out on 12 patients harboring the c.794C>T (p.

Thermal tolerance in an extremophile fish from Mexico is not affected by environmental hypoxia.

The thermal ecology of ectotherm animals has gained considerable attention in the face of human-induced climate change. Particularly in aquatic species, the experimental assessment of critical thermal limits (CTmin and CTmax) may help to predict possible effects of global warming on habitat suitability and ultimately species survival. Here we present data on the thermal limits of two endemic and endangered extremophile fish species, inhabiting a geothermally heated and sulfur-rich spring system in southern Mexico: The sulfur molly (Poecilia sulphuraria) and the widemouth gambusia (Gambusia eurystoma).

Fatty acid activation of the uncoupling proteins requires the presence of the central matrix loop from UCP1.

Noradrenaline signals the initiation of brown fat thermogenesis and the fatty acids liberated by the hormone-stimulated lipolysis act as second messengers to activate the uncoupling protein UCP1. UCP1 is a mitochondrial transporter that catalyses the re-entry of protons to the mitochondrial matrix thus allowing a regulated discharge of the proton gradient. The high affinity of UCP1 for fatty acids is a distinct feature of this uncoupling protein.

Evolutionarily distinct residues in the uncoupling protein UCP1 are essential for its characteristic basal proton conductance.

The uncoupling proteins (UCPs) are mitochondrial transporters that modulate the efficiency of oxidative phosphorylation. Members of this family have been described in many phyla within the animal and plant kingdoms, as well as in fungi. The mammalian uncoupling protein UCP1 is activated by fatty acids and inhibited by nucleotides.

Activation by retinoids of the uncoupling protein UCP1.

The uncoupling protein from brown adipose tissue (UCP1) is a transporter that catalyzes a regulated discharged of the mitochondrial proton gradient. The proton conductance in UCP1 is inhibited by nucleotides and activated by fatty acids. We have recently shown that all-trans-retinoic acid (ATRA) is a high-affinity activator of UCP1.

Alkylsulfonates activate the uncoupling protein UCP1: implications for the transport mechanism.

Fatty acids activate the uncoupling protein UCP1 by a still controversial mechanism. Two models have been put forward where the fatty acid operates as either substrate ("fatty acid cycling hypothesis") or prosthetic group ("proton buffering model"). Two sets of experiments that should help to discriminate between the two hypothetical mechanisms are presented.