Galactose is an essential carbohydrate for cellular metabolism, as it contributes to energy production and storage in several human tissues while also being a precursor for glycosylation. Galactosylated glycoconjugates, such as glycoproteins, keratan sulfate-containing proteoglycans and glycolipids, exert a plethora of biological functions, including structural support, cellular adhesion, intracellular signaling and many more. The biological relevance of galactose is further entailed by the number of pathogenic conditions consequent to defects in galactosylation and galactose homeostasis. The growing number of rare congenital disorders involving galactose along with its recent therapeutical applications are drawing increasing attention to galactose metabolism. In this review, we aim to draw a comprehensive overview of the biological functions of galactose in human cells, including its metabolism and its role in glycosylation, and to provide a systematic description of all known congenital metabolic disorders resulting from alterations of its homeostasis.
The V-ATPase is the main regulator of intra-organellar acidification. Assembly of this complex has extensively been studied in yeast, while limited knowledge exists for man. We identified 11 male patients with hemizygous missense mutations in ATP6AP1, encoding accessory protein Ac45 of the V-ATPase. Homology detection at the level of sequence profiles indicated Ac45 as the long-sought human homologue of yeast V-ATPase assembly factor Voa1. Processed wild-type Ac45, but not its disease mutants, restored V-ATPase-dependent growth in Voa1 mutant yeast. Patients display an immunodeficiency phenotype associated with hypogammaglobulinemia, hepatopathy and a spectrum of neurocognitive abnormalities. Ac45 in human brain is present as the common, processed ∼40-kDa form, while liver shows a 62-kDa intact protein, and B-cells a 50-kDa isoform. Our work unmasks Ac45 as the functional ortholog of yeast V-ATPase assembly factor Voa1 and reveals a novel link of tissue-specific V-ATPase assembly with immunoglobulin production and cognitive function.
The use of exoskeletons by the elderly, disabled people, heavy labor workers, and soldiers can have great social and economic benefit. However, limitations in usability are impeding the widespread adoption of exoskeletal devices. Kinematic compatibility, comfort, volume, mass, simplicity, expandability, and the ability to transmit forces, relative angles between the exoskeleton and the human, and the donning and doffing procedure need to be considered. Over the last decades, a large number of exoskeletons have been developed, to assert kinematic compatibility and compensate for misalignment. To such a degree, that it has become difficult to keep an overview of the different strategies. Therefore, this review article presents an extensive overview of different misalignment compensation strategies existing in the literature. Further, these strategies are organized in nine categories, evaluated and discussed around the exoskeleton's application domain and its specific requirements and needs.
11 August 2010 in International Journal of Social Robotics
Fast and accurate gait phase detection is essential to achieve effective powered lower-limb prostheses and exoskeletons. As the versatility but also the complexity of these robotic devices increases, the research on how to make gait detection algorithms more performant and their sensing devices smaller and more wearable gains interest. A functional gait detection algorithm will improve the precision, stability, and safety of prostheses, and other rehabilitation devices. In the past years the state-of-the-art has advanced significantly in terms of sensors, signal processing, and gait detection algorithms. In this review, we investigate studies and developments in the field of gait event detection methods, more precisely applied to prosthetic devices. We compared advantages and limitations between all the proposed methods and extracted the relevant questions and recommendations about gait detection methods for future developments.