Roles of AP-2 in clathrin-mediated endocytosis.

The notion that AP-2 clathrin adaptor is an essential component of an endocytic clathrin coat appears to conflict with recent observations that substantial AP-2 depletion, using RNA interference with synthesis of AP-2 subunits, fails to block uptake of certain ligands known to internalize through a clathrin-based pathway

Buses, cars, bicycles and walkers the influence of the type of human transport on the flight responses of waterbirds

One way to manage disturbance to waterbirds in natural areas where humans require access is to promote the occurrence of stimuli for which birds tolerate closer approaches, and so cause fewer responses. We conducted 730 experimental approaches to 39 species of waterbird, using five stimulus types (single walker, three walkers, bicycle, car and bus) selected to mimic different human management options available for a controlled access, Ramsar-listed wetland. Across species, where differences existed (56% of 25 cases), motor vehicles always evoked shorter flight-initiation distances (FID) than humans on foot. The influence of stimulus type on FID varied across four species for which enough data were available for complete cross-stimulus analysis. All four varied FID in relation to stimuli, differing in 4 to 7 of 10 possible comparisons. Where differences occurred, the effect size was generally modest, suggesting that managing stimulus type (e.g. by requiring people to use vehicles) may have species-specific, modest benefits, at least for the waterbirds we studied. However, different stimulus types have different capacities to reduce the frequency of disturbance (i.e. by carrying more people) and vary in their capacity to travel around important habita

Evidence for the involvement of gamma delta T cells in the immune response in Rasmussen encephalitis

Rasmussen encephalitis (RE) is a rare neuroinflammatory disease characterized by intractable seizures and progressive atrophy on one side of the cerebrum. Perivascular cuffing and clusters of T cells in the affected cortical hemisphere are indicative of an active cellular immune response. Methods: Peripheral blood mononuclear cells (PBMCs) and brain-infiltrating lymphocytes (BILs) were isolated from 20 RE surgery specimens by standard methods, and CD3+ T cell populations were analyzed by flow cytometry. Gamma delta T cell receptor spectratyping was carried out by nested PCR of reversed transcribed RNA extracted from RE brain tissue, followed by high resolution capillary electrophoresis. A MiSeq DNA sequencing platform was used to sequence the third complementarity determining region (CDR3) of δ1 chains. Results: CD3+ BILs from all of the RE brain specimens comprised both aαβ and γδ T cells. The median aαβ:γδ ratio was 1.9 (range 0.58-5.2) compared with a median ratio of 7.7 (range 2.7-40.8) in peripheral blood from the same patients. The aαβ T cells isolated from brain tissue were predominantly CD8+, and the majority of γδ T cells were CD4- CD8-. Staining for the early activation marker CD69 showed that a fraction of the aαβ and γδ T cells in the BILs were activated (median 42 %; range 13-91 %, and median 47 %; range 14-99 %, respectively). Spectratyping T cell receptor (TCR) Vδ1-3 chains from 14 of the RE brain tissue specimens indicated that the γδ T cell repertoire was relatively restricted. Sequencing δ1 chain PCR fragments revealed that the same prevalent CDR3 sequences were found in all of the brain specimens. These CDR3 sequences were also detected in brain tissue from 15 focal cortical dysplasia (FCD) cases. Conclusion: Neuroinflammation in RE involves both activated aαβ and γδ T cells. The presence of γδ T cells with identical TCR δ1 chain CDR3 sequences in all of the brain specimens examined suggests that a non-major histocompatibility complex (MHC)-restricted immune response to the same antigen(s) is involved in the etiology of RE. The presence of the same δ1 clones in CD brain implies the involvement of a common inflammatory pathway in both diseases