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.     

Diverse peptide presentation of rhesus macaque major histocompatibility complex class I Mamu-A 02 revealed by two peptide complex structures and insights into immune escape of simian immunodeficiency virus

Major histocompatibility complex class I (MHC I)-restricted CD8(+) T-cell responses play a pivotal role in anti-human immunodeficiency virus (HIV) immunity and the control of viremia. The rhesus macaque is an important animal model for HIV-related research. Among the MHC I alleles of the rhesus macaque, Mamu-A 02 is prevalent, presenting in ≥20% of macaques. In this study, we determined the crystal structure of Mamu-A 02, the second structure-determined MHC I from the rhesus macaque after Mamu-A 01. The peptide presentation characteristics of Mamu-A 02 are exhibited in complex structures with two typical Mamu-A 02-restricted CD8(+) T-cell epitopes, YY9 (Nef159 to -167; YTSGPGIRY) and GY9 (Gag71 to -79; GSENLKSLY), derived from simian immunodeficiency virus (SIV). These two peptides utilize similar primary anchor residues (Ser or Thr) at position 2 and Tyr at position 9. However, the central region of YY9 is different from that of GY9, a difference that may correlate with the immunogenic variance of these peptides. Further analysis indicated that the distinct conformations of these two peptides are modulated by four flexible residues in the Mamu-A 02 peptide-binding groove. The rare combination of these four residues in Mamu-A 02 leads to a variant presentation for peptides with different residues in their central regions. Additionally, in the two structures of the Mamu-A 02 complex, we compared the binding of rhesus and human β(2) microglobulin (β(2)m) to Mamu-A 02. We found that the peptide presentation of Mamu-A 02 is not affected by the interspecies interaction with human β(2)m. Our work broadens the understanding of CD8(+) T-cell-specific immunity against SIV in the rhesus macaque.     

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.     

In situ detection of calcium ions with chemically modified microcantilevers

We report a novel technique of micromechanical detection of trace amounts of calcium ions by using microcantilevers modified with ion-selective self-assembled monolayers (SAMs). The SAM-modified microcantilevers undergo bending due to selective adsorption of calcium ions. Experiments conducted under flow conditions show that the modified cantilevers respond sensitively to calcium ions (Ca(2+)); a Ca(2+) concentration of 10(-9) M can be detected with this technique. Other cations, such as Na(+) and K(+), do not have any effect on the deflection of these cantilevers. We demonstrate two different kinds of SAMs having selectivity for calcium ions.