Peter Schwarz

Apoptosis of macrophages and T cells in tuberculosis associated caseous necrosis.

Immunity against mycobacteria is almost exclusively confined to epithelioid cell granulomas, where a long‐lasting but labile balance exists between host and bacilli. The relationship between immunity and mycobacteria results in regression, growth, or caseation of granulomas. To prove whether caseation is associated with apoptosis, biopsy specimens of patients with tuberculosis were analysed by electron microscopy and by in situ end‐labelling combined with immunofluorescence. Apoptotic cells were not detected in regressive granulomas. Whereas productive granulomas without histologically recognizable caseous necrosis revealed only single apoptotic cells, large numbers of apoptotic CD68+ macrophages and apoptotic CD3+, CD45RO+ T cells were observed within caseous foci. As prime candidates undergoing and/or eliciting apoptosis, vital cells surrounding caseous foci were characterized. Immunohistochemistry showed that the majority of vital CD68+ macrophages surrounding caseous foci are negative for the anti‐apoptotic protein bcl2, but positive for the pro‐apoptotic protein bax. In situ hybridization combined with immunofluorescence demonstrated that the majority of the adjacent lymphocytes are activated CD3+, CD45RO+ cells expressing the pro‐inflammatory cytokine interferon γ (IFNγ) and the death ligand FasL. These results suggest that caseation is strongly associated with apoptosis of macrophages and T lymphocytes; that the onset of apoptosis in macrophages may be promoted by the lack of bcl2 and the abundance of bax; and that activation‐induced cell death (AICD) may be responsible for the apoptosis of T cells. Copyright

Autocellular coupling by gap junctions in cultured astrocytes: A new view on cellular autoregulation during process formation

Neocortical astrocytes make two types of gap junctions, intercellular ones create a functional syncytium, while reflexive gap junctions mediate autocellular coupling and serve unknown functions (Rohlmann and Wolff, 1996). Here, the question is addressed whether solitary astrocytes in vitro express connexin43 (Cx43) and establish gap junctions in the absence of intercellular contacts. In all media conditions tested, immunocytochemistry visualized Cx43‐expression and gap junctions irrespective of the presence or absence of intercellular contacts. Reflexive gap junctions were associated with mechanical junctions (adherent spots and fascia adherens) connecting surface membranes and cytoskelal components, respectively. Both were characteristically located along incompletely separated borders between developing processes and/or branches. In addition, Cx43‐immunoreactivity was found on some non‐junctional membranes: i) intracellular vesicle clusters sited to forming processes and at the basis of filopodia; ii) the surface membrane of filopodial subpopulations usually appearing in bunches. Results suggest changes in the resumptive role of Cx43 in cultivated astrocytes: 1) Cx43 is not confined to intercellular gap junctions, it may even selectively compose reflexive ones; 2) from intracellular stores (vesicle aggregates), Cx43 may be incorporated into the surface membrane of filopodia; 3) by contacting other parts of the same cell surface (or neighboring cells), filopodia and membrane patches carrying Cx43‐half channels may be essential in initial steps of gap junction formation; 4) the distribution of reflexive gap junctions is compatible with the hypothesis that autocellular coupling serves reorganization of cytoskeleton during the formation of cell processes and branches; 5) in general, gap junctions may be important for coordinating the cytoskeleton across intercellular contacts and within cells with complex shape. GLIA 24:121–140, 1998.

How Effective is the European Union's Savings Tax Directive? Evidence from Four EU Member States

This paper examines the strategies employed by individual investors to evade cross-border capital income taxation, and it evaluates the effectiveness of the EU Savings Tax Directive (STD). Using data for four European countries our results are as follows: First, individual investors adapted to the institutional changes implemented by the STD before it became effective in 2005. Second, we find that the strategy of reallocating assets from debt to equity products in the same country is more important than shifting portfolio capital out of cooperating countries into third countries. Third, countries opting for a retention tax did not experience an outflow of portfolio capital, whereas countries engaged in information exchange lost capital relative to third countries outside the scope of the STD. Finally, there is considerable heterogeneity across countries. While we find strong behavioral responses by French investors, we did not find evidence of cross border tax evasion by Italian investors, which may be explained by the absence of a national automatic reporting system on capital income in Italy. Overall, our findings show that the STD does not effectively prevent tax evasion and thus lend support to calls for tightening the directive.

Bargaining Over the Avoidance of Double Taxation: Evidence from German Tax Treaties

Previous empirical studies have mainly analyzed tax competition, neglecting the role of tax cooperation in international taxation. We focus on German double taxation agreements (DTAs) and show for up to 45 tax treaties that the bargaining outcomes depend on investment asymmetries between the countries. A transition from a purely symmetrical country pair to a situation where foreign direct investment (FDI) flows in only one direction would increase on average the negotiated withholding tax rate by roughly 5 percentage points. We also show that bargaining over DTAs is not only about withholding tax rates, but also about the definition of a permanent establishment (PE). Our results are robust with regard to the concept of investment asymmetries (either in shares or levels) and different operationalizations (FDI stocks or sales).