Genetic structure and invasion history of the house mouse (Mus musculus domesticus) in Senegal, West Africa: a legacy of colonial and contemporary times.

Knowledge of the genetic make-up and demographic history of invasive populations is critical to understand invasion mechanisms. Commensal rodents are ideal models to study whether complex invasion histories are typical of introductions involving human activities. The house mouse Mus musculus domesticus is a major invasive synanthropic rodent originating from South-West Asia. It has been largely studied in Europe and on several remote islands, but the genetic structure and invasion history of this taxon have been little investigated in several continental areas, including West Africa. In this study, we focussed on invasive populations of M. m. domesticus in Senegal. In this focal area for European settlers, the distribution area and invasion spread of the house mouse is documented by decades of data on commensal rodent communities. Genetic variation at one mitochondrial locus and 16 nuclear microsatellite markers was analysed from individuals sampled in 36 sites distributed across the country. A combination of phylogeographic and population genetics methods showed that there was a single introduction event on the northern coast of Senegal, from an exogenous (probably West European) source, followed by a secondary introduction from northern Senegal into a coastal site further south. The geographic locations of these introduction sites were consistent with the colonial history of Senegal. Overall, the marked microsatellite genetic structure observed in Senegal, even between sites located close together, revealed a complex interplay of different demographic processes occurring during house mouse spatial expansion, including sequential founder effects and stratified dispersal due to human transport along major roads.

Oxysterols regulate encephalitogenic CD4(+) T cell trafficking during central nervous system autoimmunity.

Perturbation of steroids pathways is linked to inflammation and chronic diseases, however the underlying mechanism remains unclear. Oxysterols, oxidized forms of cholesterol, are not only essential for bile synthesis and sterol transportation but have recently been shown to contribute to the immune response. In addition, serum oxysterols levels have been proposed as suitable candidate biomarkers for neurological diseases such as multiple sclerosis (MS). However how oxysterols modulate adaptive immunity is unknown and their functions in autoimmunity have not been investigated. The enzyme cholesterol 25 hydroxylase (Ch25h) is the rate limiting step to synthesize the oxysterol 7α,25-dihydroxycholesterol (7α,25-OHC) from cholesterol. We here report, using the MS murine model experimental autoimmune encephalomyelitis (EAE), that Ch25h deletion significantly attenuated EAE disease course by limiting trafficking of pathogenic CD4(+) T lymphocytes to the central nervous system (CNS). Mechanistically, we show a critical involvement for oxysterols in recruiting leukocytes into inflamed tissues and propose that 7α,25-OHC preferentially promotes the migration of activated CD44(+)CD4(+) T cells by binding the G protein-coupled receptor called Epstein-Barr virus induced gene 2 (EBI2). Collectively, our results support a pro-inflammatory role for oxysterols during EAE and identify oxysterols as a potential therapeutic target to treat autoimmune diseases.

Atmospheric physics and Earth observations: sample performance of the grille spectrometer.

The grille spectrometer observed the setting and rising sun 18 times during the Spacelab 1 mission. In addition to solar absorption lines, many of which had not been observed before, atmospheric spectral absorptions due to carbon monoxide and carbon dioxide were observed at heights tangent to the thermosphere (greater than 85 kilometers), and absorptions due to ozone, water, methane, and nitrous oxide were observed in the mesosphere (greater than 50 kilometers). The strongly coupled molecules NO-NO(2) and HC1-HF were observed as pairs in the stratosphere. Methane is presented as an example of the instrumental operations because of the characteristic aspect of the Q branch of its v(3) band.

Dual inhibition of EGFR and VEGFR pathways in combination with irradiation: antitumour supra-additive effects on human head and neck cancer xenografts.

The aim of this study was to investigate the effects of combining antiangiogenic treatment, epidermal growth factor receptor (EGFR) targeting and irradiation (RT). We evaluated AZD2171, a highly potent, orally active, vascular endothelial growth factor (VEGF) signalling inhibitor, gefitinib, an EGFR tyrosine kinase inhibitor and RT. The antitumour efficacy of these treatments, administered alone and in combination for 2 weeks, was assessed in a VEGF-secreting human head and neck tumour cell line, CAL33 that highly expresses EGFR, established as xenografts (250 mm(3)) in nude mice. The median time to reach a tumour volume of 1000 mm(3) was significantly increased for AZD2171 or gefitinib alone compared with the control. Greater inhibition of tumour growth was seen with the combination of AZD2171+gefitinib compared with either drug alone, and the triple combination compared with either AZD2171+gefitinib or RT alone. The intensity of endothelial cell staining was slightly reduced by each agent given alone, and markedly diminished by the double or triple combination. The triple combination almost completely abolished cell proliferation. The marked RT-induced enhancement in the DNA-repair enzyme ERCC1 expression was totally abolished by the triple combination. This observation could help to explain the supra-additive antitumour effect produced by this combination and could provide a basis for future innovative clinical trials.