pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis

Local extracellular acidification occurs at sites of inflammation. Proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1, also known as GPR68) responds to decreases in extracellular pH. Our previous studies show a role for OGR1 in the pathogenesis of mucosal inflammation, suggesting a link between tissue pH and immune responses. Additionally, pH-dependent signalling is associated with the progression of intestinal fibrosis. In this study, we aimed to investigate OGR1 expression and OGR1-mediated signalling in patients with inflammatory bowel disease (IBD). Our results show that OGR1 expression significantly increased in patients with IBD compared to non-IBD patients, as demonstrated by qPCR and immunohistochemistry (IHC). Paired samples from non-inflamed and inflamed intestinal areas of IBD patients showed stronger OGR1 IHC staining in inflamed mucosal segments compared to non-inflamed mucosa. IHC of human surgical samples revealed OGR1 expression in macrophages, granulocytes, endothelial cells, and fibroblasts. OGR1-dependent inositol phosphate (IP) production was significantly increased in CD14+ monocytes from IBD patients compared to healthy subjects. Primary human and murine fibroblasts exhibited OGR1-dependent IP formation, RhoA activation, F-actin, and stress fibre formation upon an acidic pH shift. OGR1 expression and signalling increases with IBD disease activity, suggesting an active role of OGR1 in the pathogenesis of IBD.     

Syngas Fermentation to Alcohols: Reactor Technology and Application Perspective

One approach of Power-to-X is the coupling of the energy and chemical sector, using electrolysis for syngas generation and microbial gas conversion for the production of biochemicals. On the verge of commercialization, known challenges of gas fermentation technology are poor mass transfer of syngas, low cell concentration and productivity. These problems can be addressed by an intelligent reactor design. Thus, this article provides an overview on the current state of the art for reactor technology in syngas fermentation and discusses possible concepts with regard to an application at industrial scale.     

Mouse Liver Compensates Loss of Sgpl1 by Secretion of Sphingolipids into Blood and Bile

Sphingosine 1 phosphate (S1P) lyase (Sgpl1) catalyses the irreversible cleavage of S1P and thereby the last step of sphingolipid degradation. Loss of Sgpl1 in humans and mice leads to accumulation of sphingolipids and multiple organ injuries. Here, we addressed the role of hepatocyte Sgpl1 for regulation of sphingolipid homoeostasis by generating mice with hepatocyte-specific deletion of Sgpl1 (Sgpl1^HepKO mice). Sgpl1^HepKO mice had normal body weight, liver weight, liver structure and liver enzymes both at the age of 8 weeks and 8 months. S1P, sphingosine and ceramides, but not glucosylceramides or sphingomyelin, were elevated by ~1.5–2-fold in liver, and this phenotype did not progress with age. Several ceramides were elevated in plasma, while plasma S1P was normal. Interestingly, S1P and glucosylceramides, but not ceramides, were elevated in bile of Sgpl1^HepKO mice. Furthermore, liver cholesterol was elevated, while LDL cholesterol decreased in 8-month-old mice. In agreement, the LDL receptor was upregulated, suggesting enhanced uptake of LDL cholesterol. Expression of peroxisome proliferator-activated receptor-γ, liver X receptor and fatty acid synthase was unaltered. These data show that mouse hepatocytes largely compensate the loss of Sgpl1 by secretion of accumulating sphingolipids in a specific manner into blood and bile, so that they can be excreted or degraded elsewhere.     

Analysis of the Material and Tablet Formation Properties of four Dioscorea Starches

The material and tablet formation properties of starches from four different Dioscorea species, namely White (D. rotundata), Bitter (D. dumetorum), Chinese (D. oppositifolia) and Water yam (D. alata), was characterized to determine their applicability as direct compression excipient. The physicochemical, thermal, morphological and material properties of the starches were investigated. The tablet formation properties were assessed using the 3‐D modeling parameters, the Heckel equation and the force‐displacement profiles. The tablet properties were evaluated using the elastic recovery and compactibility plots. The results indicate that the chemical composition, thermal and material properties of the starches varied considerably among the four species. The sorption isotherms show that the relative humidity (RH) during tablet production and storage should be carefully controlled. The tableting results show that all four starches exhibit similar time dependent deformation (d). The ranking for pressure plasticity (e) was Water > Chinese > White > Bitter, which indicates that Water deforms more easily and Bitter less easily. The ranking for fast elastic decompression was White > Water ≥ Chinese > Bitter. The amylose content, size and shape of the starch granules and specific surface area appears to play a significant role in the compressibility. Thus, White and Water with larger granules and high amylose content exhibited poor compressibility and did not form compacts except at high ρ_rel,max, while Bitter and Chinese with polygonal shape, small particle size and high specific surface area were more compressible and formed tablets of acceptable crushing force. Thus, Chinese and Bitter could be useful as excipient in direct compression.     

Biodegradable Bicomponent Fibers from Renewable Sources: Melt‐Spinning of Poly(lactic acid) and Poly[(3‐hydroxybutyrate)‐co‐(3‐hydroxyvalerate)]

PHBV is produced by bacteria as intracellular carbon storage. It is advantageous concerning biocompatibility and biodegradability, but its low crystallization rate hinders the melt‐processing of fibers. This problem can be overcome by combining PHBV with PLA in a core/sheath configuration and introducing a new spin pack concept. The resulting PHBV/PLA bicomponent fibers show an ultimate tensile stress of up to 0.34 GPa and an E‐modulus of up to 7.1 GPa. XRD reveals that PLA alone is responsible for tensile strength. In vitro biocompatibility studies with human fibroblasts reveal good cytocompatibility, making these fibers promising candidates for medical therapeutic approaches.

     

Influence of pathologic scotopization on the extended Rayleigh match

Specific antigens of virulent strains of Chlamydia psittaci isolated from ruminants were characterized by western blotting. The immunoblot analyses were performed with chlamydial elementary bodies from abortive (AB7 strain) or intestinal (iB1 strain) chlamydiae using mouse and rabbit immune sera raised against viable chlamydiae or proteic extracts. Eleven antigens were found to be AB7-specific, but only 4 (96, 90, 88 and 49-50 kDa) were recognized by both mouse and rabbit sera against viable AB7 strains. These could be candidates for specific diagnosis of caprine and ovine abortive chlamydiosis. No iB1-specific antigen recognized by mouse and rabbit anti-sera could be identified.     

Balanced Cooperative Modeling

Machine learning techniques are often used for supporting a knowledge engineer in constructing a model of part of the world. Different learning algorithms contribute to different tasks within the modeling process. Integrating several learning algorithms into one system allows it to support several modeling tasks within the same framework. In this article, we focus on the distribution of work between several learning algorithms on the one hand and the user on the other hand. The approach followed by the MOBAL system is that ofbalanced cooperation, i.e., each modeling task can be done by the user or by a learning tool of the system. The MOBAL system is described in detail. We discuss the principle of multi-functionality of one representation for the balanced use by learning algorithms and users.     

Profound neutropenia caused by oxacillin

An instance of profound neutropenia secondary to oxacillin which resolved rapidly on withdrawal of the drug was reported. It was accompanied by eosinophilia. Although the bone marrow findings were indicative of destruction of granulocytes in the periphery, antibody could not be demonstrated.     

Poly(N-acryloyl-l-prolyl morpholine): a g.p.c. packing exhibiting novel temperature dependence in solute distribution coefficients

The synthesis of $\text{poly}\text{(N-}\text{acryloyl-}\text{l}\text{-prolyl morpholine}\text{)}$, a new bead packing for the g.p.c. of small molecules, is described. Characteristic g.p.c. behaviour and high column efficiencies were observed in water and benzyl alcohol. Novel, reversible temperature variations in solute Wheaton and Bauman distribution coefficients were observed. This effect, which is most marked in water, is caused by thermo-reversible changes in network pore size distribution in the bead packing.