Terrestrial Very-Long-Baseline Atom Interferometry : summary of the second workshop

This summary of the second Terrestrial Very-Long-Baseline Atom Interferometry (TVLBAI) Workshop provides a comprehensive overview of our meeting held in London in April 2024 (Second Terrestrial Very-Long-Baseline Atom Interferometry Workshop, Imperial College, April 2024), building on the initial discussions during the inaugural workshop held at CERN in March 2023 (First Terrestrial Very-Long-Baseline Atom Interferometry Workshop, CERN, March 2023). Like the summary of the first workshop (Abend et al. in AVS Quantum Sci. 6:024701, 2024), this document records a critical milestone for the international atom interferometry community. It documents our concerted efforts to evaluate progress, address emerging challenges, and refine strategic directions for future large-scale atom interferometry projects. Our commitment to collaboration is manifested by the integration of diverse expertise and the coordination of international resources, all aimed at advancing the frontiers of atom interferometry physics and technology, as set out in a Memorandum of Understanding signed by over 50 institutions (Memorandum of Understanding for the Terrestrial Very Long Baseline Atom Interferometer Study)

Modeling tooth enamel in FEA comparisons of skulls: Comparing common simplifications with biologically realistic models

Palaeontologists often use finite element analyses, in which forces propagate through objects with specific material properties, to investigate feeding biomechanics. Teeth are usually modeled with uniform properties (all bone or all enamel). In reality, most teeth are composed of pulp, dentine, and enamel. We tested how simplified teeth compare to more realistic models using mandible models of three reptiles. For each, we created models representing enamel thicknesses found in extant taxa, as well as simplified models (bone, dentine or enamel). Our results suggest that general comparisons of stress distribution among distantly related taxa do not require representation of dental tissues, as there was no noticeable effect on heatmap representations of stress. However, we find that representation of dental tissues impacts bite force estimates, although magnitude of these effects may differ depending on constraints. Thus, as others have shown, the detail necessary in a biomechanical model relates to the questions being examined

Supplemental_Reardon_et_al – Supplemental material for Quantification of In Vivo Target Engagement Using Microfluidic Activity-Based Protein Profiling

Supplemental material, Supplemental_Reardon_et_al for Quantification of In Vivo Target Engagement Using Microfluidic Activity-Based Protein Profiling by Holly T. Reardon, Rachel A. Herbst, Cassandra L. Henry, Dylan M. Herbst, Nhi Ngo, Justin S. Cisar, Olivia D. Weber, Micah J. Niphakis and Gary P. O’Neill in SLAS Technology</p

Unexpected Phenotype Reversion and Survival in a Zebrafish Model of Multiple Sulfatase Deficiency.

Multiple sulfatase deficiency (MSD) is a rare recessively inherited Mendelian disorder that manifests with developmental delay, neurodegeneration, skeletal deformities, facial dysmorphism, congenital growth retardation, and other clinical signs. The disorder is caused by mutations in the SUMF1 gene, which encodes the formylglycine-generating enzyme (FGE), and responsible for the activation of sulfatases. Mutations in SUMF1 result in reduced or absent FGE function with consequent compromised activities of its client sulfatases. This leads to an accumulation of enzyme substrates, such as glycosaminoglycans and sulfolipids, within lysosomes and subsequently impaired lysosome function and cellular pathology. Currently, there are no disease modifying therapeutic options for MSD patients, hence the need for more suitable animal models to investigate the disorder. Here, we describe the characterisation of a sumf1 null zebrafish model, which has negligible sulfatase activity. Our sumf1 -/- zebrafish model successfully recapitulates the pathology of MSD such as cranial malformation, altered bone development, an enlarged population of microglia, and growth retardation during early development but lacks early lethality of mouse Sumf1 -/- models. Notably, we provide evidence of recovery in MSD pathology during later developmental stages, resulting in homozygous mutants that are viable. Hence, our data suggest the possibility of a unique compensatory mechanism that allows the sumf1 -/- null zebrafish to survive better than human MSD patients and mouse Sumf1 -/- models

Unexpected Phenotype Reversion and Survival in a Zebrafish Model of Multiple Sulfatase Deficiency

Multiple sulfatase deficiency (MSD) is a rare recessively inherited Mendelian disorder that manifests with developmental delay, neurodegeneration, skeletal deformities, facial dysmorphism, congenital growth retardation, and other clinical signs. The disorder is caused by mutations in the SUMF1 gene, which encodes the formylglycine-generating enzyme (FGE), and responsible for the activation of sulfatases. Mutations in SUMF1 result in reduced or absent FGE function with consequent compromised activities of its client sulfatases. This leads to an accumulation of enzyme substrates, such as glycosaminoglycans and sulfolipids, within lysosomes and subsequently impaired lysosome function and cellular pathology. Currently, there are no disease modifying therapeutic options for MSD patients, hence the need for more suitable animal models to investigate the disorder. Here, we describe the characterisation of a sumf1 null zebrafish model, which has negligible sulfatase activity. Our sumf1−/− zebrafish model successfully recapitulates the pathology of MSD such as cranial malformation, altered bone development, an enlarged population of microglia, and growth retardation during early development but lacks early lethality of mouse Sumf1−/− models. Notably, we provide evidence of recovery in MSD pathology during later developmental stages, resulting in homozygous mutants that are viable. Hence, our data suggest the possibility of a unique compensatory mechanism that allows the sumf1−/− null zebrafish to survive better than human MSD patients and mouse Sumf1−/− models.</jats:p

Phospholipase Cγ2 regulates endocannabinoid and eicosanoid networks in innate immune cells

Significance Here, we reveal that activation of phospholipase Cγ2 (PLCγ2) by disease-relevant mutations or Fc receptor signaling stimulates the production of the endocannabinoid 2-arachidonylglycerol and prostaglandins in primary human and mouse immune cells through a pathway that involves the DAG lipase (DAGL) and monoacylglycerol lipase (MGLL) enzymes. Plcg2 deficiency suppressed DAGL/MGLL-mediated endocannabinoid-eicosanoid cross-talk in mouse microglia, leading to impairment in lipopolysaccharide-mediated microglia activation in vivo that included reduced prostaglandin production and CD68 expression. Our studies provide important mechanistic insights into the regulation of lipid signaling pathways in primary immune cells, revealing a PLCγ2-DAGL-MGLL network that may serve as a future target for treating diverse immunopathologies. </jats:p

DataSheet1_Unexpected Phenotype Reversion and Survival in a Zebrafish Model of Multiple Sulfatase Deficiency.PDF

Multiple sulfatase deficiency (MSD) is a rare recessively inherited Mendelian disorder that manifests with developmental delay, neurodegeneration, skeletal deformities, facial dysmorphism, congenital growth retardation, and other clinical signs. The disorder is caused by mutations in the SUMF1 gene, which encodes the formylglycine-generating enzyme (FGE), and responsible for the activation of sulfatases. Mutations in SUMF1 result in reduced or absent FGE function with consequent compromised activities of its client sulfatases. This leads to an accumulation of enzyme substrates, such as glycosaminoglycans and sulfolipids, within lysosomes and subsequently impaired lysosome function and cellular pathology. Currently, there are no disease modifying therapeutic options for MSD patients, hence the need for more suitable animal models to investigate the disorder. Here, we describe the characterisation of a sumf1 null zebrafish model, which has negligible sulfatase activity. Our sumf1−/− zebrafish model successfully recapitulates the pathology of MSD such as cranial malformation, altered bone development, an enlarged population of microglia, and growth retardation during early development but lacks early lethality of mouse Sumf1−/− models. Notably, we provide evidence of recovery in MSD pathology during later developmental stages, resulting in homozygous mutants that are viable. Hence, our data suggest the possibility of a unique compensatory mechanism that allows the sumf1−/− null zebrafish to survive better than human MSD patients and mouse Sumf1−/− models.</p