The Roles of Hypoxia-Inducible Factors in Regulating Neural Stem Cells Migration to Glioma Stem Cells and Determinating Their Fates

The mortality of patients with malignant gliomas remains high despite the advancement in multi-modal therapy including surgery, radio- and chemotherapy. Glioma stem cells (GSCs), sharing some characteristics with normal neural stem cells (NSCs), contribute to the cellular origin for primary gliomas and the recurrence of malignant gliomas after current conventional therapy. Accordingly, targeting GSCs proves to be a promising avenue of therapeutic intervention. The specific tropism of NSCs to GSCs provides a novel platform for targeted delivery of therapeutic agents. Tropism and mobilization of NSCs are enhanced by hypoxia through upregulating chemotactic cytokines and activating several signaling pathways. Moreover, hypoxia-inducible factors (HIFs) produced under hypoxic microenvironment of the stem cell niche play critical roles in the growth and stemness phenotypes regulation of both NSCs and GSCs. However, the definite cellular and molecular mechanisms of HIFs involvement in the process remain obscure. In this review, we focus on the pivotal roles of HIFs in migration of NSCs to GSCs and potential roles of HIFs in dictating the fates of migrated NSCs and targeted GSCs.     

Parasites paralyze cellular host defense system to promote virulence

To promote their survival, intracellular pathogens must confront microbicidal activities induced by interferons. In this issue of Cell Host & Microbe, Fentress et?al. show that Toxoplasma gondii evades intracellular killing by deploying a virulence determinant, ROP18, which acts by directly phosphorylating and disabling an IFN-γ-inducible immunity-related GTPase involved in pathogen clearance.     

Microbiological and production characteristics of the high-temperature Kongdian bed revealed during field trial of biotechnology for the enhancement of oil recovery

Microbiological technology for the enhancement of oil recovery based on the activation of the stratal microflora was tested in the high-temperature horizons of the Kongdian bed (60 degrees C) of the Dagang oil field (China). This biotechnology consists in the pumping of a water-air mixture and nitrogen and phosphorus mineral salts into the oil stratum through injection wells in order to stimulate the activity of the stratal microflora which produce oil-releasing metabolites. Monitoring of the physicochemical, microbiological, and production characteristics of the test site has revealed large changes in the ecosystem as a result of the application of biotechnology. The cell numbers of thermophilic hydrocarbon-oxidizing, fermentative, sulfate-reducing, and methanogenic microorganisms increased 10-10 000-fold. The rates of methanogenesis and sulfate reduction increased in the near-bottom zone of the injection wells and of some production wells. The microbial oil transformation was accompanied by the accumulation of bicarbonate ions, volatile fatty acids, and biosurfactants in the formation waters, as well as of CH4 and CO2 both in the gas phase and in the oil. Microbial metabolites promoted the additional recovery of oil. As a result of the application of biotechnology, the water content in the production liquid from the test site decreased, and the oil content increased. This allowed the recovery of more than 14000 tons of additional oil over 3.5 years.     

A profile of the residues in the second extracellular loop that are critical for ligand recognition of human prostacyclin receptor

The residues in the second extracellular loop (eLP2) of the prostanoid receptors, which are important for specific ligand recognition, were previously predicted in our earlier studies of the thromboxane A2 receptor (TP) using a combination of NMR spectroscopy and recombinant protein approaches. To further test this hypothesis, another prostanoid receptor, the prostacyclin receptor (IP), which has opposite biological characteristics to that of TP, was used as a model for these studies. A set of recombinant human IPs with site-directed mutations at the nonconserved eLP2 residues were constructed using an Ala-scanning approach, and then expressed in HEK293 and COS-7 cells. The expression levels of the recombinant receptors were six-fold higher in HEK293 cells than in COS-7 cells. The residues important for ligand recognition and binding within the N-terminal segment (G159, Q162, and C165) and the C-terminal segment (L172, R173, M174, and P179) of IP eLP2 were identified by mutagenesis analyses. The molecular mechanisms for the specific ligand recognition of IP were further demonstrated by specific site-directed mutagenesis using different amino acid residues with unique chemical properties for the key residues Q162, L172, R173, and M174. A comparison with the corresponding functional residues identified in TP eLP2 revealed that three (Q162, R173, and M174) of the four residues are nonconserved, and these are proposed to be involved in specific ligand recognition. We discuss the importance of G159 and P179 in ligand recognition through configuration of the loop conformation is discussed. These studies have further indicated that characterization of the residues in the eLP2 regions for all eight prostanoid receptors could be an effective approach for uncovering the molecular mechanisms of the ligand selectivities of the G-protein-coupled receptors.