Ubiquitin-protein ligase Ubr5 cooperates with hedgehog signalling to promote skeletal tissue homeostasis

Mammalian Hedgehog (HH) signalling pathway plays an essential role in tissue homeostasis and its deregulation is linked to rheumatological disorders. UBR5 is the mammalian homologue of the E3 ubiquitin-protein ligase Hyd, a negative regulator of the Hh-pathway in Drosophila. To investigate a possible role of UBR5 in regulation of the musculoskeletal system through modulation of mammalian HH signaling, we created a mouse model for specific loss of Ubr5 function in limb bud mesenchyme. Our findings revealed a role for UBR5 in maintaining cartilage homeostasis and suppressing metaplasia. Ubr5 loss of function resulted in progressive and dramatic articular cartilage degradation, enlarged, abnormally shaped sesamoid bones and extensive heterotopic tissue metaplasia linked to calcification of tendons and ossification of synovium. Genetic suppression of smoothened (Smo), a key mediator of HH signalling, dramatically enhanced the Ubr5 mutant phenotype. Analysis of HH signalling in both mouse and cell model systems revealed that loss of Ubr5 stimulated canonical HH-signalling while also increasing PKA activity. In addition, human osteoarthritic samples revealed similar correlations between UBR5 expression, canonical HH signalling and PKA activity markers. Our studies identified a crucial function for the Ubr5 gene in the maintenance of skeletal tissue homeostasis and an unexpected mode of regulation of the HH signalling pathway.     

The transmittable through stinging microbiota differs between honeybees and wasps: a potentially greater microbial risk of the wasp sting for humans

International Microbiology -     

Biogenic calcite particles from microalgae—Coccoliths as a potential raw material

Synthetic calcite (CaCO₃) particles are found in a broad range of applications. The geometry of particles produced from limestone or precipitation are versatile but limited to basic shapes. The microalga Emiliania huxleyi produces micro‐structured calcite platelets, called coccoliths. This article presents the results of an application‐orientated study, which includes characteristic values also used in the calcite industry for particle evaluation. It is demonstrated that coccoliths are significantly different from all industrial particles produced so far. Coccoliths are porous particles, mainly consisted of calcium carbonate, with further elements such as Mg, Si, Sr, and Fe often embedded in their structure. Their structure is extremely sophisticated, while the overall particle morphology and particle size distribution are homogeneous. This study gives a first inside into the potential of these exceptional objects and may set further impulses for their utilization in specific calcite particle applications.     

Differences in Survival among 13 Listeria monocytogenes Strains in a Dynamic Model of the Stomach and Small Intestine

Thirteen Listeria monocytogenes strains were compared for the ability to survive in a dynamic gastrointestinal model. Strains displayed various degrees of susceptibility to gastric acidity; however, strain-to-strain variations became evident mainly after 90 min of exposure (pH 2.0). Cell levels transferred to the intestine depended on initial populations, while reductions during intestinal exposure were relatively small for all strains.     

TIMP-1 interaction with αvβ3 integrin confers resistance to human osteosarcoma cell line MG-63 against TNF-α-induced apoptosis

Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine affecting diverse cellular responses. TNF-α is cytotoxic in many systems, but it can also act as an anti-apoptotic signal to promote cell survival pathways activated through integrins and extracellular matrix components. This is particularly evident in cancer cells. To unravel the basis of resistance to TNF-α-induced apoptosis, human osteosarcoma MG-63 cell line was used. Our data showed that resistance to apoptosis was accompanied by high levels of TIMP-1 expression in part mediated by NF-κB activation, whereas under apoptotic conditions, in the presence of cycloheximide (CHX), TIMP-1 and αvβ3 integrin protein levels were significantly reduced. Silencing TIMP-1 using siRNA led to increased apoptosis following treatment with TNF-α, whereas exogenously-added recombinant TIMP-1 reduced the extent of apoptosis. Immunoprecipitation and confocal microscopy experiments demonstrated that TIMP-1 interacted with αvβ3 integrins. The biological role of this interaction was revealed by the use of echistatin, an antagonist of αvβ3 integrin. In the presence of echistatin, decreased protection against apoptosis by recombinant TIMP-1 was observed.     

Study of multiparameter respiratory pattern complexity in surgical critically ill patients during weaning trials

Background  

Separation from mechanical ventilation is a difficult task, whereas conventional predictive indices have not been proven accurate enough, so far. A few studies have explored changes of breathing pattern variability for weaning outcome prediction, with conflicting results. In this study, we tried to assess respiratory complexity during weaning trials, using different non-linear methods derived from theory of complex systems, in a cohort of surgical critically ill patients.