The Cerebral Microvasculature in Schizophrenia: A Laser Capture Microdissection Study

BACKGROUND: Previous studies of brain and peripheral tissues in schizophrenia patients have indicated impaired energy supply to the brain. A number of studies have also demonstrated dysfunction of the microvasculature in schizophrenia patients. Together these findings are consistent with a hypothesis of blood-brain barrier dysfunction in schizophrenia. In this study, we have investigated the cerebral vascular endothelium of schizophrenia patients at the level of transcriptomics. METHODOLOGY/PRINCIPAL FINDINGS: We used laser capture microdissection to isolate both microvascular endothelial cells and neurons from post mortem brain tissue from schizophrenia patients and healthy controls. RNA was isolated from these cell populations, amplified, and analysed using two independent microarray platforms, Affymetrix HG133plus2.0 GeneChips and CodeLink Whole Human Genome arrays. In the first instance, we used the dataset to compare the neuronal and endothelial data, in order to demonstrate that the predicted differences between cell types could be detected using this methodology. We then compared neuronal and endothelial data separately between schizophrenic subjects and controls. Analysis of the endothelial samples showed differences in gene expression between schizophrenics and controls which were reproducible in a second microarray platform. Functional profiling revealed that these changes were primarily found in genes relating to inflammatory processes. CONCLUSIONS/SIGNIFICANCE: This study provides preliminary evidence of molecular alterations of the cerebral microvasculature in schizophrenia patients, suggestive of a hypo-inflammatory state in this tissue type. Further investigation of the blood-brain barrier in schizophrenia is warranted

Islam, identity and professional values: A study of journalists in three Muslim-majority regions

Abstract: Islam is a religion, but it is also a philosophy. An analysis of surveys in the Arab world, Indonesia and Pakistan reveals that the mission and values of journalists in those Muslim-majority regions closely track Islamic obligations to tell the truth, seek justice and work toward the public interest. This article provides empirical data to bolster the argument that the values of Islam are the prism through which journalists in Muslim-majority countries approach their profession. Those findings add to the body of research supporting the theory that journalistic norms are contextual, shaped by a hierarchy of influences that include global standards and local values such as culture, political climate and religion. But the findings also indicate that in regions where a professional journalistic culture is in the process of emerging, the influence of personal versus professional values is in reverse proportion to those found in more mature journalistic markets

Dissimilar flexibility of alpha and beta subunits of human adult hemoglobin influences the protein dynamics and its alteration induced by allosteric effectors

The general question by what mechanism an "effector" molecule and the hemes of hemoglobin interact over widely separated intramolecular distances to change the oxygen affinity has been extensively investigated, and still has remained of central interest. In the present work we were interested in clarifying the general role of the protein matrix and its dynamics in the regulation of human adult hemoglobin (HbA). We used a spectroscopy approach that yields the compressibility (kappa) of the protein matrix around the hemes of the subunits in HbA and studied how the binding of heterotropic allosteric effectors modify this parameter. kappa is directly related to the variance of volume fluctuation, therefore it characterizes the molecular dynamics of the protein structure. For the experiments the heme groups either in the alpha or in the beta subunits of HbA were replaced by fluorescent Zn-protoporphyrinIX, and series of fluorescence line narrowed spectra were measured at varied pressures. The evaluation of the spectra yielded the compressibility that showed significant dynamic asymmetry between the subunits: kappa of the alpha subunit was 0.17+/-0.05/GPa, while for the beta subunit it was much higher, 0.36+/-0.07/GPa. The heterotropic effectors, chloride ions, inositol hexaphosphate and bezafibrate did not cause significant changes in kappa of the alpha subunits, while in the beta subunits the effectors lead to a significant reduction down to 0.15+/-0.04/GPa. We relate our results to structural data, to results of recent functional studies and to those of molecular dynamics simulations, and find good agreements. The observed asymmetry in the flexibility suggests a distinct role of the subunits in the regulation of Hb that results in the observed changes of the oxygen binding capability