Perceiving and acting upon weight illusions in the absence of somatosensory information

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this record.When lifting novel objects, individuals’ fingertip forces are influenced by a variety of cues such as volume and apparent material. This means that heavy-looking objects tend to be lifted with more force than lighter-looking objects, even when they weigh the same amount as one another. Expectations about object weight based on visual appearance also influence how heavy an object feels when it is lifted. For instance, in the "size-weight illusion," small objects feel heavier than equally weighted large objects. Similarly, in the "material-weight illusion," objects that seem to be made from light-looking materials feel heavier than objects of the same weight that appear to be made from heavy-looking materials. In this study, we investigated these perceptual and sensorimotor effects in IW, an individual with peripheral deafferentation (i.e., a loss of tactile and proprioception feedback). We examined his perceptions of heaviness and fingertip force application over repeated lifts of objects that varied in size or material properties. Despite being able to report real weight differences, IW did not appear to experience the size- or material-weight illusions. Furthermore, he showed no evidence of sensorimotor prediction based on size and material cues. The results are discussed in the context of forward models and their possible influence on weight perception and fingertip force control

Studies on the factors involved in the secretion of enzymic and non-enzymic contents of rat liver lysosomes

The aim of this present study has been to investigate the role of microfilaments in the secretion of lysosomal enzymes from rat liver cells and the effect, if any, on this process of changes in the intralysosomal environment. Using the systems of short-term rat hepatocyte cultures and isolated rat liver prefusions, the effect of the microfilament poison, cytochalasin B, on the secretion of the lysosomal enzymes aryIsulphatase A + B, B-galactosidase and, in some instances, beta-N-acetyl-glucos-aminidase has been examined. In addition, the release of the cytosol enzyme lactate dehydrogenase was monitored to determine non-specific enzyme release due to cell damage. The intralysosomal environment was modified by pre-loading the liver lysosomes in vivo with a variety of macromolecular materials, i.e. 125I-polyvinylpyrrolidone,H-dextran and 125I-Triton WR-1339. The effect of this lysosomal modificationon the release of the lysosomal enzymes and its modulation of the effect of microfilament disruption, as induced by cytochalasin B, as well as the effect of this disruption on the release of the preloaded materials, was determined. In addition, the intracellular distribution of these preloaded materials in the rat liver was investigated before, and in some cases after, the livers had been perfused. Attempts were made to correlate the heterogeneity of the density-gradient-centrifugation profiles of the preloaded, intralysosomal materials and those of the various lysosomal enzymes with their heterogeneous secretion patterns during perfusion in the presence and the absence of cytochalasin B. Preliminary attempts were made to delineate the contributions of secretion (exocytcsis) and reuptake (endo-cytosis) in the net "appearance" of both the enzymic and non-enzymic lysosomal contents in the perfusate. From the results obtained a hypothesis was formulated which suggested that the intralysosomal presence of non-enzymatic material, does indeed modulate not only the "base-line" secretion of lysosomal enzymes, but also the effect of microfilament disruption on this process. This modulation could involve modifications to the lysosomal membrane, such that it might fuse more readily with the plasma membrane.<p

Effects of Pairing in the Pseudo-SU(3) Model

An extended version of the pseudo-SU(3) model which includes both spin and proton-neutron degrees of freedom is used to study the influence of the pairing interaction on K-band mixing, B(E2) values and quadrupole moments. Using the asymmetric rotor model as a backdrop, specific consequences of a many-particle shell-model based description of these collective properties are demonstrated and fundamental limits of the collective model's approach are investigated. Finally, the pseudo-SU(3) model, including representation mixing induced by pairing, is used to calculate the energies of 140Ce and the results are compared to experimental data and other theories.Comment: 21 pages, Latex, 11 figures available on request via mail or fax, accepted by Nucl. Phys.

Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder due to the deficient activity of the acid beta-glucosidase (GCase) enzyme, resulting in the progressive lysosomal accumulation of glucosylceramide (GlcCer) and its deacylated derivate, glucosylsphingosine (GlcSph). GCase is encoded by the GBA1 gene, located on chromosome 1q21 16 kb upstream from a highly homologous pseudogene. To date, more than 400 GBA1 pathogenic variants have been reported, many of them derived from recombination events between the gene and the pseudogene. In the last years, the increased access to new technologies has led to an exponential growth in the number of diagnostic laboratories offering GD testing. However, both biochemical and genetic diagnosis of GD are challenging and to date no specific evidence-based guidelines for the laboratory diagnosis of GD have been published. The objective of the guidelines presented here is to provide evidence-based recommendations for the technical implementation and interpretation of biochemical and genetic testing for the diagnosis of GD to ensure a timely and accurate diagnosis for patients with GD worldwide. The guidelines have been developed by members of the Diagnostic Working group of the International Working Group of Gaucher Disease (IWGGD), a non-profit network established to promote clinical and basic research into GD for the ultimate purpose of improving the lives of patients with this disease. One of the goals of the IWGGD is to support equitable access to diagnosis of GD and to standardize procedures to ensure an accurate diagnosis. Therefore, a guideline development group consisting of biochemists and geneticists working in the field of GD diagnosis was established and a list of topics to be discussed was selected. In these guidelines, twenty recommendations are provided based on information gathered through a systematic review of the literature and two different diagnostic algorithms are presented, considering the geographical differences in the access to diagnostic services. Besides, several gaps in the current diagnostic workflow were identified and actions to fulfill them were taken within the IWGGD. We believe that the implementation of recommendations provided in these guidelines will promote an equitable, timely and accurate diagnosis for patients with GD worldwide

Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1

: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder due to the deficient activity of the acid beta-glucosidase (GCase) enzyme, resulting in the progressive lysosomal accumulation of glucosylceramide (GlcCer) and its deacylated derivate, glucosylsphingosine (GlcSph). GCase is encoded by the GBA1 gene, located on chromosome 1q21 16 kb upstream from a highly homologous pseudogene. To date, more than 400 GBA1 pathogenic variants have been reported, many of them derived from recombination events between the gene and the pseudogene. In the last years, the increased access to new technologies has led to an exponential growth in the number of diagnostic laboratories offering GD testing. However, both biochemical and genetic diagnosis of GD are challenging and to date no specific evidence-based guidelines for the laboratory diagnosis of GD have been published. The objective of the guidelines presented here is to provide evidence-based recommendations for the technical implementation and interpretation of biochemical and genetic testing for the diagnosis of GD to ensure a timely and accurate diagnosis for patients with GD worldwide. The guidelines have been developed by members of the Diagnostic Working group of the International Working Group of Gaucher Disease (IWGGD), a non-profit network established to promote clinical and basic research into GD for the ultimate purpose of improving the lives of patients with this disease. One of the goals of the IWGGD is to support equitable access to diagnosis of GD and to standardize procedures to ensure an accurate diagnosis. Therefore, a guideline development group consisting of biochemists and geneticists working in the field of GD diagnosis was established and a list of topics to be discussed was selected. In these guidelines, twenty recommendations are provided based on information gathered through a systematic review of the literature and two different diagnostic algorithms are presented, considering the geographical differences in the access to diagnostic services. Besides, several gaps in the current diagnostic workflow were identified and actions to fulfill them were taken within the IWGGD. We believe that the implementation of recommendations provided in these guidelines will promote an equitable, timely and accurate diagnosis for patients with GD worldwide

Toward understanding tissue-specific symptoms in dolichol-phosphate-mannose synthesis disorders; insight from DPM3-CDG

Contains fulltext : 208143.pdf (publisher's version ) (Open Access

a-Synuclein and lipids in erythrocytes of Gaucher disease carriers and patients before and after enzyme replacement therapy

It is well established that patients with Gaucher disease, as well as carriers of the disease have an increased risk for developing Parkinson's disease. A plethora of evidence suggests that disturbed alpha-Synuclein homeostasis is the link between Gaucher disease and Parkinson's disease. The pathogenic mechanism linking these entities is still a topic of debate and both gain- and loss-of-function theories have been put forward, which however are not mutually exclusive. In the present study we expanded our previous studies to include not only Gaucher disease patients but also Gaucher disease carriers and Gaucher disease patients following Enzyme Replacement Therapy. In these groups we investigated alpha-Synuclein in red blood cell membranes in association with lipid abnormalities described in Gaucher disease. These included glucosylceramide and its species, glucosylsphingosine, glucosylcholesterol and plasmalogens. Increased oligomerization of alpha-Synuclein in red blood cell membranes was observed not only in Gaucher disease patients but also in carriers of the disease. There were no qualitative differences in the lipids identified in the groups studied. However, significant quantitative differences compared to controls were observed in Gaucher disease patients but not in Gaucher disease carriers. Enzyme Replacement Therapy reversed the biochemical defects and normalized alpha-Synuclein homeostasis, providing for the first time evidence in human subjects that such homeostatic dysregulation is reversible. Further studies investigating alpha-Synuclein status during the differentiation of erythroid progenitors could provide new data on the pathogenic mechanism of alpha-Synuclein oligomerization in this system.Medical Biochemistr

Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder due to the deficient activity of the acid beta-glucosidase (GCase) enzyme, resulting in the progressive lysosomal accumulation of glucosylceramide (GlcCer) and its deacylated derivate, glucosylsphingosine (GlcSph). GCase is encoded by the GBA1 gene, located on chromosome 1q21 16 kb upstream from a highly homologous pseudogene. To date, more than 400 GBA1 pathogenic variants have been reported, many of them derived from recombination events between the gene and the pseudogene. In the last years, the increased access to new technologies has led to an exponential growth in the number of diagnostic laboratories offering GD testing. However, both biochemical and genetic diagnosis of GD are challenging and to date no specific evidence-based guidelines for the laboratory diagnosis of GD have been published. The objective of the guidelines presented here is to provide evidence-based recommendations for the technical implementation and interpretation of biochemical and genetic testing for the diagnosis of GD to ensure a timely and accurate diagnosis for patients with GD worldwide. The guidelines have been developed by members of the Diagnostic Working group of the International Working Group of Gaucher Disease (IWGGD), a non-profit network established to promote clinical and basic research into GD for the ultimate purpose of improving the lives of patients with this disease. One of the goals of the IWGGD is to support equitable access to diagnosis of GD and to standardize procedures to ensure an accurate diagnosis. Therefore, a guideline development group consisting of biochemists and geneticists working in the field of GD diagnosis was established and a list of topics to be discussed was selected. In these guidelines, twenty recommendations are provided based on information gathered through a systematic review of the literature and two different diagnostic algorithms are presented, considering the geographical differences in the access to diagnostic services. Besides, several gaps in the current diagnostic workflow were identified and actions to fulfill them were taken within the IWGGD. We believe that the implementation of recommendations provided in these guidelines will promote an equitable, timely and accurate diagnosis for patients with GD worldwide.Instituto de Estudios Inmunológicos y Fisiopatológico