Live imaging reveals a conserved role of fatty acid beta-oxidation in early lymphatic development in zebrafish

During embryonic development, lymphatic endothelial cells (LECs) differentiate from venous endothelial cells (VECs), a process that is tightly regulated by several genetic signals. While the aquatic zebrafish model is regularly used for studying lymphangiogenesis and offers the unique advantage of time-lapse video-imaging of lymphatic development, some aspects of lymphatic development in this model differ from those in the mouse. It therefore remained to be determined whether fatty acid β-oxidation (FAO), which we showed to regulate lymphatic formation in the mouse, also co-determines lymphatic development in this aquatic model. Here, we took advantage of the power of the zebrafish embryo model to visualize the earliest steps of lymphatic development through time-lapse video-imaging. By targeting zebrafish isoforms of carnitine palmitoyltransferase 1a (cpt1a), a rate controlling enzyme of FAO, with multiple morpholinos, we demonstrate that reducing CPT1A levels and FAO flux during zebrafish development impairs lymphangiogenic secondary sprouting, the initiation of lymphatic development in the zebrafish trunk, and the formation of the first lymphatic structures. These findings not only show evolutionary conservation of the importance of FAO for lymphatic development, but also suggest a role for FAO in co-regulating the process of VEC-to-LEC differentiation in zebrafish in vivo.status: publishe

An introductory study of house spiders (Araneae) in Belgium

More than 800 spiders were collected in 43 houses heated in winter, distributed mainly in the northern part of Belgium. Information required for the collections to be eligible for the project was: address, construction year, type of house, and surroundings. The spiders were qualified as ‘house spiders’ or ‘garden spiders’. Of the 93 species collected, 19 could be defined as house spiders. Pholcus phalangioides was the most common,followed by Eratigena atrica and Steatoda triangulosa. Garden spiders enter the house much more often in houses in a rural environment than in those situated in clusters, and mainly in spring. The spiders are most common in autumn when many of them are breeding. The common house spiders colonize houses shortly after their construction

Notch3 Arg170Cys Knock-In Mice Display Pathologic and Clinical Features of the Neurovascular Disorder Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

OBJECTIVE-: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset neurovascular disorder caused by stereotyped mutations in the NOTCH3 receptor. Elucidation of its pathobiology is still incomplete and remains a challenge, in part because the available preclinical mouse models to date do not reproduce the full spectrum of CADASIL pathology and clinical disease. METHODS AND RESULTS-: Here, we report a novel knock-in mouse with Arg170Cys substitution in murine Notch3, corresponding to the prevalent Arg169Cys substitution in CADASIL. The Notch3 mice displayed late-onset, dominant CADASIL arteriopathy with typical granular osmiophilic material deposition and developed brain histopathology including thrombosis, microbleeds, gliosis, and microinfarction. Furthermore, Notch3 mice experienced neurological symptoms with motor defects such as staggering gait and limb paresis. CONCLUSION-: This model, for the first time, phenocopies the arteriopathy and the histopathologic as well as clinical features of CADASIL and may offer novel opportunities to investigate disease pathogenesis.status: publishe

An introductory study of house spiders (Araneae) in Belgium

More than 800 spiders were collected in 43 houses heated in winter, distributed mainly in the northern part of Belgium. Information required for the collections to be eligible for the project was: address, construction year, type of house, and surroundings. The spiders were qualified as ‘house spiders’ or ‘garden spiders’. Of the 93 species collected, 19 could be defined as house spiders. Pholcus phalangioides was the most common,followed by Eratigena atrica and Steatoda triangulosa. Garden spiders enter the house much more often in houses in a rural environment than in those situated in clusters, and mainly in spring. The spiders are most common in autumn when many of them are breeding. The common house spiders colonize houses shortly after their construction

The gluconeogenesis enzyme PCK2 has a non-enzymatic role in proteostasis in endothelial cells

Abstract Endothelial cells (ECs) are highly glycolytic, but whether they generate glycolytic intermediates via gluconeogenesis (GNG) in glucose-deprived conditions remains unknown. Here, we report that glucose-deprived ECs upregulate the GNG enzyme PCK2 and rely on a PCK2-dependent truncated GNG, whereby lactate and glutamine are used for the synthesis of lower glycolytic intermediates that enter the serine and glycerophospholipid biosynthesis pathways, which can play key roles in redox homeostasis and phospholipid synthesis, respectively. Unexpectedly, however, even in normal glucose conditions, and independent of its enzymatic activity, PCK2 silencing perturbs proteostasis, beyond its traditional GNG role. Indeed, PCK2-silenced ECs have an impaired unfolded protein response, leading to accumulation of misfolded proteins, which due to defective proteasomes and impaired autophagy, results in the accumulation of protein aggregates in lysosomes and EC demise. Ultimately, loss of PCK2 in ECs impaired vessel sprouting. This study identifies a role for PCK2 in proteostasis beyond GNG