University of Zurich

About: University of Zurich is a education organization based out in Zurich, Switzerland. It is known for research contribution in the topics: Population & Transplantation. The organization has 50842 authors who have published 124042 publications receiving 5304521 citations. The organization is also known as: UZH & Uni Zurich.

Visual navigation in insects: coupling of egocentric and geocentric information

Abstract: Social hymenopterans such as bees and ants are central-place foragers; they regularly depart from and return to fixed positions in their environment. In returning to the starting point of their foraging excursion or to any other point, they could resort to two fundamentally different ways of navigation by using either egocentric or geocentric systems of reference. In the first case, they would rely on information continuously collected en route (path integration, dead reckoning), i.e. integrate all angles steered and all distances covered into a mean home vector. In the second case, they are expected, at least by some authors, to use a map-based system of navigation, i.e. to obtain positional information by virtue of the spatial position they occupy within a larger environmental framework. In bees and ants, path integration employing a skylight compass is the predominant mechanism of navigation, but geocentred landmark-based information is used as well. This information is obtained while the animal is dead-reckoning and, hence, added to the vector course. For example, the image of the horizon skyline surrounding the nest entrance is retinotopically stored while the animal approaches the goal along its vector course. As shown in desert ants (genus Cataglyphis), there is neither interocular nor intraocular transfer of landmark information. Furthermore, this retinotopically fixed, and hence egocentred, neural snapshot is linked to an external (geocentred) system of reference. In this way, geocentred information might more and more complement and potentially even supersede the egocentred information provided by the path-integration system. In competition experiments, however, Cataglyphis never frees itself of its homeward-bound vector - its safety-line, so to speak - by which it is always linked to home. Vector information can also be transferred to a longer-lasting (higher-order) memory. There is no need to invoke the concept of the mental analogue of a topographic map - a metric map - assembled by the insect navigator. The flexible use of vectors, snapshots and landmark-based routes suffices to interpret the insect's behaviour. The cognitive-map approach in particular, and the representational paradigm in general, are discussed.

Combined Measurement and QCD Analysis of the Inclusive e± p Scattering Cross Sections at HERA

Abstract: A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e(+/-)p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q(2), and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result.

MEK1 mutations confer resistance to MEK and B-RAF inhibition

Abstract: Genetic alterations that activate the mitogen-activated protein kinase (MAP kinase) pathway occur commonly in cancer. For example, the majority of melanomas harbor mutations in the BRAF oncogene, which are predicted to confer enhanced sensitivity to pharmacologic MAP kinase inhibition (e.g., RAF or MEK inhibitors). We investigated the clinical relevance of MEK dependency in melanoma by massively parallel sequencing of resistant clones generated from a MEK1 random mutagenesis screen in vitro, as well as tumors obtained from relapsed patients following treatment with AZD6244, an allosteric MEK inhibitor. Most mutations conferring resistance to MEK inhibition in vitro populated the allosteric drug binding pocket or α-helix C and showed robust (≈100-fold) resistance to allosteric MEK inhibition. Other mutations affected MEK1 codons located within or abutting the N-terminal negative regulatory helix (helix A), which also undergo gain-of-function germline mutations in cardio-facio-cutaneous (CFC) syndrome. One such mutation, MEK1(P124L), was identified in a resistant metastatic focus that emerged in a melanoma patient treated with AZD6244. Both MEK1(P124L) and MEK1(Q56P), which disrupts helix A, conferred cross-resistance to PLX4720, a selective B-RAF inhibitor. However, exposing BRAF-mutant melanoma cells to AZD6244 and PLX4720 in combination prevented emergence of resistant clones. These results affirm the importance of MEK dependency in BRAF-mutant melanoma and suggest novel mechanisms of resistance to MEK and B-RAF inhibitors that may have important clinical implications.