Sex, Ecology and the Brain: Evolutionary Correlates of Brain Structure Volumes in Tanganyikan Cichlids

Analyses of the macroevolutionary correlates of brain structure volumes allow pinpointing of selective pressures influencing specific structures. Here we use a multiple regression framework, including phylogenetic information, to analyze brain structure evolution in 43 Tanganyikan cichlid species. We analyzed the effect of ecological and sexually selected traits for species averages, the effect of ecological traits for each sex separately and the influence of sexual selection on structure dimorphism. Our results indicate that both ecological and sexually selected traits have influenced brain structure evolution. The patterns observed in males and females generally followed those observed at the species level. Interestingly, our results suggest that strong sexual selection is associated with reduced structure volumes, since all correlations between sexually selected traits and structure volumes were negative and the only statistically significant association between sexual selection and structure dimorphism was also negative. Finally, we previously found that monoparental female care was associated with increased brain size. However, here cerebellum and hypothalamus volumes, after controlling for brain size, associated negatively with female-only care. Thus, in accord with the mosaic model of brain evolution, brain structure volumes may not respond proportionately to changes in brain size. Indeed selection favoring larger brains can simultaneously lead to a reduction in relative structure volumes

Influence of O6-benzylguanine on the anti-tumour activity and normal tissue toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea and molecular combinations of 5-fluorouracil and 2-chloroethyl-1-nitrosourea in mice

Previous studies have demonstrated that novel molecular combinations of 5-fluorouracil (5FU) and 2-chloroethyl-1-nitrosourea (CNU) have good preclinical activity and may exert less myelotoxicity than the clinically used nitrosoureas such as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). This study examined the effect of O6-alkylguanine-DNA-alkyltransferase (ATase) depletion by the pseudosubstrate O6-benzylguanine (BG) on the anti-tumour activity and normal tissue toxicity in mice of three such molecular combinations, in comparison with BCNU. When used as single agents at their maximum tolerated dose, all three novel compounds produced a significant growth retardation of BCNU-resistant murine colon and human breast xenografts. This in vivo anti-tumour effect was potentiated by BG, but was accompanied by severe myelotoxicity as judged by spleen colony forming assays. However, while tumour resistance to BCNU was overcome using BG, this was at the expense of enhanced bone marrow, gut and liver toxicity. Therefore, although this ATase-depletion approach resulted in improved anti-tumour activity for all three 5-FU:CNU molecular combinations, the potentiated toxicities in already dose-limiting tissues indicate that these types of agents offer no therapeutic advantage over BCNU when they are used together with BG. © 1999 Cancer Research Campaig

Direct stau production at hadron colliders in cosmologically motivated scenarios

We calculate dominant cross section contributions for stau pair production at hadron colliders within the MSSM, taking into account left-right mixing of the stau eigenstates. We find that b-quark annihilation and gluon fusion can enhance the cross sections by more than one order of magnitude with respect to the Drell-Yan predictions. These additional production channels are not yet included in the common Monte Carlo analysis programs and have been neglected in experimental analyses so far. For long-lived staus, we investigate differential distributions and prospects for their stopping in the collider detectors. New possible strategies are outlined to determine the mass and width of the heavy CP-even Higgs boson H0. Scans of the relevant regions in the CMSSM are performed and predictions are given for the current experiments at the LHC and the Tevatron. The obtained insights allow us to propose collider tests of cosmologically motivated scenarios with long-lived staus that have an exceptionally small thermal relic abundance.Comment: 49 pages, 13 figures; v2: references added, typos corrected, text streamlined, results unchange

Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer

The degree of damage to DNA following ifosfamide (IFO) treatment may be linked to the therapeutic efficacy. The pharmacokinetics and metabolism of IFO were studied in 19 paediatric patients, mostly with rhabdomyosarcoma or Ewings sarcoma. Ifosfamide was dosed either as a continuous infusion or as fractionated doses over 2 or 3 days. Samples of peripheral blood lymphocytes were obtained during and up to 96 h after treatment, and again prior to the next cycle of chemotherapy. DNA damage was measured using the alkaline COMET assay, and quantified as the percentage of highly damaged cells per sample. Samples were also taken for the determination of IFO and metabolites. Pharmacokinetics and metabolism of IFO were comparable with previous studies. Elevations in DNA damage could be determined in all patients after IFO administration. The degree of damage increased to a peak at 72 h, but had returned to pretreatment values prior to the next dose of chemotherapy. There was a good correlation between area under the curve of IFO and the cumulative percentage of cells with DNA damage (r2 = 0.554, P = 0.004), but only in those patients receiving fractionated dosing. The latter patients had more DNA damage (mean ± s.d., 2736 ± 597) than those patients in whom IFO was administered by continuous infusion (1453 ± 730). The COMET assay can be used to quantify DNA damage following IFO therapy. Fractionated dosing causes a greater degree of DNA damage, which may suggest a greater degree of efficacy, with a good correlation between pharmacokinetic and pharmacodynamic data

Release of engineered nanomaterials from personal care products throughout their life cycle

The impetus for this study was to provide release estimates that can serve to improve predictions of engineered nanomaterial (ENM) exposure for risk assessment. We determined the likely release of ENMs from personal care products (PCPs) through a consumer survey on use and disposal habits, and research on the types and quantities of ENMs in PCPs. Our estimates show that in the US zinc oxide (ZnO), with 1,800-2,100 mt yr-1, and titanium dioxide (TiO2), with 870-1,000 mt yr-1, represent 94 % of ENMs released into the environment or landfills from the use of PCPs. Around 36-43 % of ENMs from PCPs were estimated to end up in landfills, 24-36 % released to soils, 0.7-0.8 % to air, and 28-32 % to water bodies. ENMs in sunscreen represent around 81-82 % of total release, from ZnO and TiO2 as UV blockers, followed by facial moisturizer (7.5 %), foundation (5.7 %), and hair coloring products (3.1 %). Daily care products such as body wash, shampoo, and conditioner had by far the highest per capita and total use, but contributed little to the ENM release estimates as these products generally contain little or no ENMs. However, if ENMs are incorporated into these daily care products, this may substantially increase ENM release. © 2014 Springer Science+Business Media

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Searches for heavy long-lived charged particles with the ATLAS detector in proton-proton collisions at √s = 8 TeV

Searches for heavy long-lived charged particles are performed using a data sample of 19.1 fb−1 from proton-proton collisions at a centre-of-mass energy of s√ = 8 TeV collected by the ATLAS detector at the Large Hadron Collider. No excess is observed above the estimated background and limits are placed on the mass of long-lived particles in various supersymmetric models. Long-lived tau sleptons in models with gauge-mediated symmetry breaking are excluded up to masses between 440 and 385 GeV for tan β between 10 and 50, with a 290 GeV limit in the case where only direct tau slepton production is considered. In the context of simplified LeptoSUSY models, where sleptons are stable and have a mass of 300 GeV, squark and gluino masses are excluded up to a mass of 1500 and 1360 GeV, respectively. Directly produced charginos, in simplified models where they are nearly degenerate to the lightest neutralino, are excluded up to a mass of 620 GeV. R-hadrons, composites containing a gluino, bottom squark or top squark, are excluded up to a mass of 1270, 845 and 900 GeV, respectively, using the full detector; and up to a mass of 1260, 835 and 870 GeV using an approach disregarding information from the muon spectrometer