General laboratory diagnostics of eosinophilic GI diseases

Eosinophils and gastrointestinal tract interact in an intimate and enigmatic relationship. Under inflammatory conditions, eosinophil infiltration in the gastrointestinal tract is a common feature of numerous eosinophilic gastrointestinal disorders (EGIDs). EGIDs are disorders, for which the diagnosis is relatively difficult. Nevertheless, some common laboratory techniques are currently used for their diagnosis and disease monitoring. Besides eosinophils, mast cells and T cells have also been suggested to play a role in the pathogenesis of these disorders. Here, we review the pathogenesis and common laboratory approaches applied for their diagnosis, in particular eosinophil and mast cell markers.

Inhibition of dendritic Ca2+ spikes by GABAB receptors in cortical pyramidal neurons is mediated by a direct Gi/o- -subunit interaction with Cav1 channels

Voltage-dependent calcium channels (VDCCs) serve a wide range of physiological functions and their activity is modulated by different neurotransmitter systems. GABAergic inhibition of VDCCs in neurons has an important impact in controlling transmitter release, neuronal plasticity, gene expression and neuronal excitability. We investigated the molecular signalling mechanisms by which GABAB receptors inhibit calcium-mediated electrogenesis (Ca2+ spikes) in the distal apical dendrite of cortical layer 5 pyramidal neurons. Ca2+ spikes are the basis of coincidence detection and signal amplification of distal tuft synaptic inputs characteristic for the computational function of cortical pyramidal neurons. By combining dendritic whole-cell recordings with two-photon fluorescence Ca2+ imaging we found that all subtypes of VDCCs were present in the Ca2+ spike initiation zone, but that they contribute differently to the initiation and sustaining of dendritic Ca2+ spikes. Particularly, Cav1 VDCCs are the most abundant VDCC present in this dendritic compartment and they generated the sustained plateau potential characteristic for the Ca2+ spike. Activation of GABAB receptors specifically inhibited Cav1 channels. This inhibition of L-type Ca2+ currents was transiently relieved by strong depolarization but did not depend on protein kinase activity. Therefore, our findings suggest a novel membrane-delimited interaction of the Gi/o-βγ-subunit with Cav1 channels identifying this mechanism as the general pathway of GABAB receptor-mediated inhibition of VDCCs. Furthermore, the characterization of the contribution of the different VDCCs to the generation of the Ca2+ spike provides new insights into the molecular mechanism of dendritic computation.

Vegetation responses to rapid warming and to minor climatic fluctuations during the Late-Glacial Interstadial (GI-1) at Gerzensee (Switzerland)

High-resolution pollen analyses made on the same samples on which the ratios of oxygen isotopes were measured that provided the time scale and a temperature proxy after correlation to NorthGRIP. (1) A primary succession: The vegetation responded to the rapid rise of temperatures around 14,685 yr BP, with a primary succession on a decadal to centennial time scale. The succession between ca 15,600 and 13,000 yr BP included: (1.1.) The replacement of shrub-tundra by woodland of Juniperus and tree birch (around 14,665 yr BP) (1.2.) The response of Juniperus pollen to the shift in oxygen isotopes in less than 20 yr, (1.3.) A sequence of population increases of Hippophaë rhamnoides (ca 14,600 yr BP), Salix spp. (ca 14,600 yr BP), Betula trees (ca.14,480 yr BP), Populus cf. tremula (ca. 14,300 yr BP), and Pinus cf. sylvestris (ca. 13,830 yr BP). (2) Biological processes: Plants responded to the rapid increase of summer temperatures on all organisational levels: (2.1) Individuals may have produced more pollen (e.g. Juniperus); (2.2) Populations increased or decreased (e.g. Juniperus, Betula, later Pinus), and (2.3) Populations changed their biogeographical range and may show migrational lags. (2.4) Plant communities changed in their composition because the species pools changed through immigration and (local) extinction. Some plant communities may have been without modern analogue.These mechanisms require increasing amounts of time. (2.5) Processes on the level of ecosystems, with species interactions, may involve various time scales. Besides competition and facilitation, nitrogen fixation is discussed. (3) The minor fluctuations of temperature during the Late-Glacial Interstadial, which are recorded in δ18O, resulted in only very minor changes in pollen during the Aegelsee Oscillation (Older Dryas biozone, GI-1d) and the Gerzensee Oscillation (GI-1b). (4) Biodiversity: The afforestation at the onset of Bølling coincided with a gradual increase of taxonomic diversity up to the time of the major Pinus expansion.