Cell spheroid viscoelasticity is deformation-dependent.

Tissue surface tension influences cell sorting and tissue fusion. Earlier mechanical studies suggest that multicellular spheroids actively reinforce their surface tension with applied force. Here we study this open question through high-throughput microfluidic micropipette aspiration measurements on cell spheroids to identify the role of force duration and spheroid deformability.

Animal Models for the Study of Gaucher Disease.

In Gaucher disease (GD), a relatively common sphingolipidosis, the mutant lysosomal enzyme acid β-glucocerebrosidase (GCase), encoded by the gene, fails to properly hydrolyze the sphingolipid glucosylceramide (GlcCer) in lysosomes, particularly of tissue macrophages. As a result, GlcCer accumulates, which, to a certain extent, is converted to its deacylated form, glucosylsphingosine (GlcSph), by lysosomal acid ceramidase. The inability of mutant GCase to degrade GlcSph further promotes its accumulation.

The development of a broad-spectrum retaining β-exo-galactosidase activity-based probe.

Acid β-galactosidase (GLB1) and galactocerebrosidase (GALC) are retaining exo-β-galactosidases involved in lysosomal glycoconjugate metabolism. Deficiency of GLB1 may result in the lysosomal storage disorders GM1 gangliosidosis, Morquio B syndrome, and galactosialidosis, and deficiency of GALC may result in Krabbe disease. Activity-based protein profiling (ABPP) is a powerful technique to assess the activity of retaining glycosidases in relation to health and disease.

High-throughput mechanophenotyping of multicellular spheroids using a microfluidic micropipette aspiration chip.

Cell spheroids are multicellular model systems that mimic the crowded micro-environment of biological tissues. Their mechanical characterization can provide valuable insights in how single-cell mechanics and cell-cell interactions control tissue mechanics and self-organization. However, most measurement techniques are limited to probing one spheroid at a time, require specialized equipment and are difficult to handle.

Defaunation changes leaf trait composition of recruit communities in tropical forests in French Guiana.

Hunting impacts tropical vertebrate populations, causing declines of species that function as seed dispersers and predators, or that browse seedlings and saplings. Whether and how the resulting reductions in seed dispersal, seed predation, and browsing translate to changes in the tree composition is poorly understood. Here, we assess the effect of defaunation on the functional composition of communities of tree recruits in tropical rainforests in French Guiana.

Consequences of excessive glucosylsphingosine in glucocerebrosidase-deficient zebrafish.

In Gaucher disease (GD), the deficiency of glucocerebrosidase causes lysosomal accumulation of glucosylceramide (GlcCer), which is partly converted by acid ceramidase to glucosylsphingosine (GlcSph) in the lysosome. Chronically elevated blood and tissue GlcSph is thought to contribute to symptoms in GD patients as well as to increased risk for Parkinson's disease. On the other hand, formation of GlcSph may be beneficial since the water soluble sphingoid base is excreted via urine and bile.

HEPES-buffering of bicarbonate-containing culture medium perturbs lysosomal glucocerebrosidase activity.

Glucocerebrosidase (GCase), encoded by the GBA gene, degrades the ubiquitous glycosphingolipid glucosylceramide. Inherited GCase deficiency causes Gaucher disease (GD). In addition, carriers of an abnormal GBA allele are at increased risk for Parkinson's disease.

Xylose-Configured Cyclophellitols as Selective Inhibitors for Glucocerebrosidase.

Glucocerebrosidase (GBA), a lysosomal retaining β-d-glucosidase, has recently been shown to hydrolyze β-d-xylosides and to transxylosylate cholesterol. Genetic defects in GBA cause the lysosomal storage disorder Gaucher disease (GD), and also constitute a risk factor for developing Parkinson's disease. GBA and other retaining glycosidases can be selectively visualized by activity-based protein profiling (ABPP) using fluorescent probes composed of a cyclophellitol scaffold having a configuration tailored to the targeted glycosidase family.

Fabry Disease: Molecular Basis, Pathophysiology, Diagnostics and Potential Therapeutic Directions.

Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by the deficiency of α-galactosidase A (α-GalA) and the consequent accumulation of toxic metabolites such as globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3). Early diagnosis and appropriate timely treatment of FD patients are crucial to prevent tissue damage and organ failure which no treatment can reverse. LSDs might profit from four main therapeutic strategies, but hitherto there is no cure.

Tree mode of death and mortality risk factors across Amazon forests.

The carbon sink capacity of tropical forests is substantially affected by tree mortality. However, the main drivers of tropical tree death remain largely unknown. Here we present a pan-Amazonian assessment of how and why trees die, analysing over 120,000 trees representing > 3800 species from 189 long-term RAINFOR forest plots.

Lyso-glycosphingolipids: presence and consequences.

Lyso-glycosphingolipids are generated in excess in glycosphingolipid storage disorders. In the course of these pathologies glycosylated sphingolipid species accumulate within lysosomes due to flaws in the respective lipid degrading machinery. Deacylation of accumulating glycosphingolipids drives the formation of lyso-glycosphingolipids.

Manno--cyclophellitols Enable Activity-Based Protein Profiling of Human α-Mannosidases and Discovery of New Golgi Mannosidase II Inhibitors.

Golgi mannosidase II (GMII) catalyzes the sequential hydrolysis of two mannosyl residues from GlcNAcManGlcNAc to produce GlcNAcManGlcNAc, the precursor for all complex -glycans, including the branched -glycans associated with cancer. Inhibitors of GMII are potential cancer therapeutics, but their usefulness is limited by off-target effects, which produce α-mannosidosis-like symptoms. Despite many structural and mechanistic studies of GMII, we still lack a potent and selective inhibitor of this enzyme.

Glycosphingolipids and Infection. Potential New Therapeutic Avenues.

Glycosphingolipids (GSLs), the main topic of this review, are a subclass of sphingolipids. With their glycans exposed to the extracellular space, glycosphingolipids are ubiquitous components of the plasma membrane of cells. GSLs are implicated in a variety of biological processes including specific infections.

Timing of repair and mesh use in traumatic abdominal wall defects: a systematic review and meta-analysis of current literature.

Background: Traumatic abdominal wall hernias or defects (TAWDs) after blunt trauma are rare and comprehensive literature on this topic is scarce. Altogether, there is no consensus about optimal methods and timing of repair, resulting in a surgeon's dilemma. The aim of this study was to analyze current literature, comparing (1) acute versus delayed repair and (2) mesh versus no mesh repair.

Evolutionary diversity is associated with wood productivity in Amazonian forests.

Higher levels of taxonomic and evolutionary diversity are expected to maximize ecosystem function, yet their relative importance in driving variation in ecosystem function at large scales in diverse forests is unknown. Using 90 inventory plots across intact, lowland, terra firme, Amazonian forests and a new phylogeny including 526 angiosperm genera, we investigated the association between taxonomic and evolutionary metrics of diversity and two key measures of ecosystem function: aboveground wood productivity and biomass storage. While taxonomic and phylogenetic diversity were not important predictors of variation in biomass, both emerged as independent predictors of wood productivity.

The Iminosugar AMP-DNM Improves Satiety and Activates Brown Adipose Tissue Through GLP1.

Obesity is taking on worldwide epidemic proportions, yet effective pharmacological agents with long-term efficacy remain unavailable. Previously, we designed the iminosugar N-adamantine-methyloxypentyl-deoxynojirimycin (AMP-DNM), which potently improves glucose homeostasis by lowering excessive glycosphingolipids. Here we show that AMP-DNM promotes satiety and activates brown adipose tissue (BAT) in obese rodents.

Role of β-glucosidase 2 in aberrant glycosphingolipid metabolism: model of glucocerebrosidase deficiency in zebrafish.

β-glucosidases [GBA1 (glucocerebrosidase) and GBA2] are ubiquitous essential enzymes. Lysosomal GBA1 and cytosol-facing GBA2 degrade glucosylceramide (GlcCer); GBA1 deficiency causes Gaucher disease, a lysosomal storage disorder characterized by lysosomal accumulation of GlcCer, which is partly converted to glucosylsphingosine (GlcSph). GBA1 and GBA2 also may transfer glucose from GlcCer to cholesterol, yielding glucosylated cholesterol (GlcChol).

Management strategies and outcome of blunt traumatic abdominal wall defects: a single centre experience.

Introduction: Traumatic abdominal wall defects (TAWDs) following blunt trauma are uncommon injuries with an incidence reported less than 1%. Improved diagnostics and subsequent early detection of otherwise rare injuries raise more questions concerning their treatment. There is lack of consensus on treatment and timing of TAWD.

Influence of livelihood assets, experienced shocks and perceived risks on smallholder coffee farming practices in Peru.

Smallholder farmers might adopt different farming practices to cope with multiple stressors depending on their livelihood assets, and with varying environmental and economic outcomes. Ongoing global change is triggering stronger and different stressors that threaten conventional farming practices; however, this could be resolved if livelihood assets that drive decision making are actionable and thus can be modified. This study assessed the influence of farmers' livelihood assets, risk perception, and shocks on the choice of non-conventional farming practices for smallholder coffee farmers in San Martín, Peru.

Development of multi locus sequence typing (MLST) of Rodentibacter pneumotropicus.

The aim of the investigation was to develop a definitive typing system for Rodentibacter pneumotropicus. A total of 79 strains including the type strain of R. pneumotropicus, all associated with rodents were used to develop a multi-locus sequence typing scheme (MLST).