hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33

The completion of the Human Genome Project resulted in discovery of many unknown novel genes. This feat paved the way for the future development of novel therapeutics for the treatment of human disease based on novel biological functions and pathways. Towards this aim, we undertook a bioinformatics analysis of in-house microarray data derived from purified hematopoietic stem cell populations. This effort led to the discovery of HSS1 (Hematopoietic Signal peptide-containing Secreted 1) and its splice variant HSM1 (Hematopoietic Signal peptide-containing Membrane domain-containing 1). HSS1 gene is evolutionarily conserved across species, phyla and even kingdoms, including mammals, invertebrates and plants. Structural analysis showed no homology between HSS1 and known proteins or known protein domains, indicating that it was a truly novel protein. Interestingly, the human HSS1 (hHSS1) gene is located at chromosome 19q13.33, a genomic region implicated in various cancers, including malignant glioma. Stable expression of hHSS1 in glioma-derived A172 and U87 cell lines greatly reduced their proliferation rates compared to mock-transfected cells. hHSS1 expression significantly affected the malignant phenotype of U87 cells both in vitro and in vivo. Further, preliminary immunohistochemical analysis revealed an increase in hHSS1/HSM1 immunoreactivity in two out of four high-grade astrocytomas (glioblastoma multiforme, WHO IV) as compared to low expression in all four low-grade diffuse astrocytomas (WHO grade II). High-expression of hHSS1 in high-grade gliomas was further supported by microarray data, which indicated that mesenchymal subclass gliomas exclusively up-regulated hHSS1. Our data reveal that HSS1 is a truly novel protein defining a new class of secreted factors, and that it may have an important role in cancer, particularly glioma

A New Horned Crocodile from the Plio-Pleistocene Hominid Sites at Olduvai Gorge, Tanzania

BACKGROUND: The fossil record reveals surprising crocodile diversity in the Neogene of Africa, but relationships with their living relatives and the biogeographic origins of the modern African crocodylian fauna are poorly understood. A Plio-Pleistocene crocodile from Olduvai Gorge, Tanzania, represents a new extinct species and shows that high crocodylian diversity in Africa persisted after the Miocene. It had prominent triangular "horns" over the ears and a relatively deep snout, these resemble those of the recently extinct Malagasy crocodile Voay robustus, but the new species lacks features found among osteolaemines and shares derived similarities with living species of Crocodylus. METHODOLOGY/PRINCIPAL FINDINGS: The holotype consists of a partial skull and skeleton and was collected on the surface between two tuffs dated to approximately 1.84 million years (Ma), in the same interval near the type localities for the hominids Homo habilis and Australopithecus boisei. It was compared with previously-collected material from Olduvai Gorge referable to the same species. Phylogenetic analysis places the new form within or adjacent to crown Crocodylus. CONCLUSIONS/SIGNIFICANCE: The new crocodile species was the largest predator encountered by our ancestors at Olduvai Gorge, as indicated by hominid specimens preserving crocodile bite marks from these sites. The new species also reinforces the emerging view of high crocodylian diversity throughout the Neogene, and it represents one of the few extinct species referable to crown genus Crocodylus

Dangerous Air: How air pollution affects astrocyte functions

Outdoor air pollution is the largest environmental risk factor that has been associated with cardiovascular, lung, and lately also neurodegenerative diseases. A few studies have been conducted to demonstrate that air pollutant exposure may lead to neuroinflammation, oxidative stress and the appearance of protein aggregates in the brain. It was shown that air pollution can cause not only peripheral effects, but airborne particles can also enter the brain directly through olfactory nerve road or enter the blood circulation. Therefore, there is an unmet need for understanding how different brain cell types are involved in this pathological process. In this study, we aim to decipher how size-segregated urban particulate matter (PM) that was collected from urban air in Nanjing, China affects astrocytes and their functions and to investigate genes that could be targeted to mitigate the adverse effect of PM exposure. Our results demonstrate that both ultrafine (particles with an aerodynamic diameter of 0.1 μm or less) and coarse (size 2.5-10 μm) particles trigger activation of antioxidative stress signalling genes in vitro in astrocytes harvested from the adult mouse brain, indicating activation of the cellular protection system in response to PM. Such robust effects were not observed in primary cortical neurons exposed to the same conditions, indicating the predominant role of glial cell responses to adverse effects of air pollution in the brain. We also detected reduced ApoE expression in both adult and neonatal PM-treated astrocytes in response to PM exposure. These results provide insight into astrocyte responses to air pollutant exposure

Taking the chance: Core self-evaluations predict relative gain in job resources following turnover

Core self-evaluations (CSE) might account for relative gains in job resources across time, especially in situations when these individual differences affect behavior that is relevant for development of job resources. This longitudinal study tests CSE as an individual resource that predicts relative gain in job resources and job satisfaction among job beginners who change or stay with their employer. A questionnaire was filled in by 513 adolescents shortly before the end of vocational training and one year later. Our results replicate previous findings suggesting that job satisfaction is affected by CSE directly and indirectly through the perception of job resources. Multi-group structural equation analysis showed that only leavers had a longitudinal indirect effect of CSE on job satisfaction at the end of vocational training via job resources during their first year of employment. Our findings imply that turnover includes opportunities to optimize one’s circumstances and that CSE helps to attain resourceful jobs