Isolated rat hepatocytes can signal to other hepatocytes and bile duct cells by release of nucleotides.

Intercellular communication among certain cell types can occur via ATP secretion, which leads to stimulation of nucleotide receptors on target cells. In epithelial cells, however, intercellular communication is thought to occur instead via gap junctions. Here we examined whether one epithelial cell type, hepatocytes, can also communicate via nucleotide secretion. The effects on cytosolic Ca2+ ([Ca2+]i) of mechanical stimulation, including microinjection, were examined in isolated rat hepatocytes and in isolated bile duct units using confocal fluorescence video microscopy. Mechanical stimulation of a single hepatocyte evoked an increase in [Ca2+]i in the stimulated cell plus an unexpected [Ca2+]i rise in neighboring noncontacting hepatocytes. Perifusion with ATP before mechanical stimulation suppressed the [Ca2+]i increase, but pretreatment with phenylephrine did not. The P2 receptor antagonist suramin inhibited these intercellular [Ca2+]i signals. The ATP/ADPase apyrase reversibly inhibited the [Ca2+]i rise induced by mechanical stimulation, and did not block vasopressin-induced [Ca2+]i signals. Mechanical stimulation of hepatocytes also induced a [Ca2+]i increase in cocultured isolated bile duct units, and this [Ca2+]i increase was inhibited by apyrase as well. Finally, this form of [Ca2+]i signaling could be elicited in the presence of propidium iodide without nuclear labeling by that dye, indicating that this phenomenon does not depend on disruption of the stimulated cell. Thus, mechanical stimulation of isolated hepatocytes, including by microinjection, can evoke [Ca2+]i signals in the stimulated cell as well as in neighboring noncontacting hepatocytes and bile duct epithelia. This signaling is mediated by release of ATP or other nucleotides into the extracellular space. This is an important technical consideration given the widespread use of microinjection techniques for examining mechanisms of signal transduction. Moreover, the evidence provided suggests a novel paracrine signaling pathway for epithelia, which previously were thought to communicate exclusively via gap junctions.

Evolutionary conservation of human TATA-binding-polypeptide-associated factors TAFII31 and TAFII80 and interactions of TAFII80 with other TAFs and with general transcription factors.

Human transcription initiation factor TFIID is composed of the TATA-binding polypeptide (TBP) and at least 13 TBP-associated factors (TAFs) that collectively or individually are involved in activator-dependent transcription. To investigate protein-protein interactions involved in TFIID assembly and in TAF-mediated activator functions, we have cloned and expressed cDNAs encoding human TAFII80 and TAFII31. Coimmunoprecipitation assays showed that TAFII80 interacted with TAFII250, TAFII31, TAFII20, and TBP, but not with TAFII55. Similar assays showed that TAFII80 interacted with TFIIE alpha and with TFIIF alpha (RAP74) but not with TFIIB, TFIIE beta, or TFIIF beta (RAP30). Further studies with TAFII80 mutations revealed three distinct interaction domains which fall within regions conserved in human TAFII80, Drosophila TAFII60, and yeast TAFII60. The N terminus of TAFII80 (residues 1-100) interacts with both TAFII31 and TAFII20, while two C-terminal regions are involved, respectively, in interactions with TAFII250 and TFIIF alpha (RAP74) (residues 203-276) and with TBP and TFIIE alpha (residues 377-505). The interactions between TAFII80 and general factors TFIIE alpha and TFIIF alpha (RAP74) could be important for recruitment of GTFs during activator-dependent transcription. Because TAFs 80, 31, and 20 show sequence similarities to histones H4, H3, and H2B, as well as some parallel interactions, this subset of TAFs may form a related core structure within TFIID.

Characterizations of logarithmic Besov spaces in terms of differences, Fourier-analytical decompositions, wavelets and semi-groups.

We work with Besov spaces Bp,q0,b defined by means of differences, with zero classical smoothness and logarithmic smoothness with exponent b. We characterize Bp,q0,b by means of Fourier-analytical decompositions, wavelets and semi-groups. We also compare those results with the well-known characterizations for classical Besov spaces Bp,qs.

Racism, Other Discriminations and Effects on Health

We study the probability of perceived racism/other forms of discrimination on immigrant and Spanish populations within different public spheres and show their effect on the health of immigrants using a cross-sectional design (ENS-06). Variables: perceived racism/other forms of discrimination (exposure), socio-demographic (explicative), health indicators (dependent). Frequencies, prevalences, and bivariate/multivariate analysis were conducted separately for men (M) and women (W). We estimated the health problems attributable to racism through the population attributable proportion (PAP). Immigrants perceived more racism than Spaniards in workplace (ORM = 48.1; 95 % CI 28.2–82.2), and receiving health care (ORW = 48.3; 95 % CI 24.7–94.4). Racism and other forms of discrimination were associated with poor mental health (ORM = 5.6; 95 % CI 3.9–8.2; ORW = 7.3; 95 % CI 4.1–13.0) and injury (ORW = 30.6; 95 % CI 13.6–68.7). It is attributed to perceived racism the 80.1 % of consumption of psychotropics (M), and to racism with other forms of discrimination the 52.3 % of cases of injury (W). Racism plays a role as a health determinant.

The Euro Crisis, the Other Crisis and the Need for Global Thinking

In addition to the euro crisis the EU faces a second, more existential crisis, in the form of an ill-defined notion of the Union’s global role. This contribution argues that the euro crisis should not redefine perceptions of the EU on the global stage, which it is in danger of doing. Instead, the EU and its members should embark upon a strategic reassessment in order to define three core interrelated factors. First, the nature of the EU’s actorness remains ill-defined and it is therefore necessary to explain, both within and beyond the Union, what its global role is. Second, in order to facilitate the joining up of the myriad of sub-strategies in EU external relations, the notion of ‘red lines’ should be considered which define specific aspects of behaviour that are mainstreamed throughout the EU’s external actions and, more importantly, upheld. Third, in spite of the rapid development of the harder elements of the EU’s actorness over the last decade or so, there remains a worrying gap between rhetoric and reality. This aspect is of particular concern for the United States and will affect perceptions of the EU’s ability to be a genuine strategic partner at a time of dramatic change in the international system. By engaging in what will inevitably be a difficult debate, the EU and its members will not only help give purpose and strategic direction to the Union’s actions on the international scene, it will also speak to the euro crisis since both are fundamentally about the future shape and direction of European integration.