Calcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation

Nicotinic acid adenine dinucleotide phosphate (NAADP) has been implicated as an initial Ca(2+) trigger in T cell Ca(2+) signalling, but its role in formation of the immune synapse in CD4(+) effector T cells has not been analysed. CD4(+) T cells are activated by the interaction with peptide-MHCII complexes on the surface of antigen-presenting cells. Establishing a two-cell system including primary rat CD4(+) T cells specific for myelin basic protein and rat astrocytes enabled us to mirror this activation process in vitro and to analyse Ca(2+) signalling, cell shape changes and motility in T cells during formation and maintenance of the immune synapse. After immune synapse formation, T cells showed strong, antigen-dependent increases in free cytosolic calcium concentration ([Ca(2+)](i)). Analysis of cell shape and motility revealed rounding and immobilization of T cells depending on the amplitude of the Ca(2+) signal. NAADP-antagonist BZ194 effectively blocked Ca(2+) signals in T cells evoked by the interaction with antigen-presenting astrocytes. BZ194 reduced the percentage of T cells showing high Ca(2+) signals thereby supporting the proposed trigger function of NAADP for global Ca(2+) signalling. Taken together, the NAADP signalling pathway is further confirmed as a promising target for specific pharmacological intervention to modulate T cell activation

All dried up: the materiality of drought in Ladismith, South Africa

This paper conceptualizes droughts as socioecological phenomena coproduced by the recursive engagement of human and non-human transformations. Through an interdisciplinary approach that integrates political ecology, material geographies and hydroclimatology, this work simultaneously apprehends the role of politics and power in reshaping drought, along with the agency of biophysical processes —soil, vegetation, hydrology and microclimate— that co-produce droughts and their spatiotemporal patterning. The drought-stricken Ladismith in Western Cape, South Africa, is the instrumental case study and point of departure of our empirical analysis. To advance a materiality of drought that seriously accounts for the coevolution of biophysical and political transformations, we alter the spatiotemporal and empirical foci of drought analyses thereby retracing Ladismith’s socioecological history since colonial times. In turn, such extended framework exposes the agency of soil, vegetation, hydrology and microclimate and their metabolic exchanges with processes of colonization, apartheid, capitalist and neoliberal transformations of South African economy. We argue that the narrow pursuit of profits and capital accumulation of the few has produced a fundamental disruption between nature and society which contributed to transform Ladismith’s drought into a socioecological crisis. Whilst advancing debates on materiality, we note two fundamental contributions to the study of drought. First, our approach makes hydrological accounts of droughts less politically naive and socially blind. Second, it develops a political ecology of droughts and socioecological crises more attuned to the materiality of drought. We contend that apprehending the materiality of drought and the active role of its non-human processes can further understandings of the workings of power and the production of socioecological injustices

Aggregatibacter actinomycetemcomitans Omp29 Is Associated with Bacterial Entry to Gingival Epithelial Cells by F-Actin Rearrangement

The onset and progressive pathogenesis of periodontal disease is thought to be initiated by the entry of Aggregatibacter actinomycetemcomitans (Aa) into periodontal tissue, especially gingival epithelium. Nonetheless, the mechanism underlying such bacterial entry remains to be clarified. Therefore, this study aimed to investigate the possible role of Aa outer membrane protein 29 kD (Omp29), a homologue of E. coli OmpA, in promoting bacterial entry into gingival epithelial cells. To accomplish this, Omp29 expression vector was incorporated in an OmpA-deficient mutant of E. coli. Omp29+/OmpA− E. coli demonstrated 22-fold higher entry into human gingival epithelial line cells (OBA9) than Omp29−/OmpA− E. coli. While the entry of Aa and Omp29+/OmpA− E. coli into OBA9 cells were inhibited by anti-Omp29 antibody, their adherence to OBA9 cells was not inhibited. Stimulation of OBA9 cells with purified Omp29 increased the phosphorylation of focal adhesion kinase (FAK), a pivotal cell-signaling molecule that can up-regulate actin rearrangement. Furthermore, Omp29 increased the formation of F-actin in OBA9 cells. The internalization of Omp29-coated beads and the entry of Aa into OBA9 were partially inhibited by treatment with PI3-kinase inhibitor (Wortmannin) and Rho GTPases inhibitor (EDIN), both known to convey FAK-signaling to actin-rearrangement. These results suggest that Omp29 is associated with the entry of Aa into gingival epithelial cells by up-regulating F-actin rearrangement via the FAK signaling pathway

Stratigraphic correlation and paleoenvironmental analysis of the hydrocarbon-bearing Early Miocene Euphrates and Jeribe formations in the Zagros folded-thrust belt

The Lower Miocene Euphrates and Jeribe formations are considered as the main targets of the Tertiary petroleum system in the western part of the Zagros Basin. The formations consist of carbonates with some evaporate intercalations of the Dhiban Formation. This study utilized data from a field investigation including newly described outcrop sections and newly discovered productive oil fields within the Kirkuk embayment zone of the Zagros fold and thrust belt such as Sarqala and Kurdamir wells. This work is the first to show a stratigraphic correlation and paleoenvironmental interpretation by investigating both well data and new outcrop data. Three depositional environments were identified, (1) an inner and outer ramp belts environment, (2) shoal environment, and (3) restricted lagoon environment. Within these 3 environments, 12 microfacies were identified, based on the distribution of fauna mainly benthonic foraminifera, rock textures, and sedimentary structures. The inferred shallow water depths and variable salinities in both the Euphrates Formation and Jeribe Formation carbonates are consistent with deposition on the inner ramp (restricted lagoon and shoal) environments. Those found in the Euphrates Formation constrained the depositional environment to the restricted lagoon and shoal environment, while the microfacies in the Jeribe Formation provided evidence for an inner ramp and middle to outer ramp belt environments. This study represents the first detailed research that focuses on the stratigraphic correlation and changes in carbonate facies with the main aim to provide a wider understanding of stratigraphy of these carbonate reservoirs throughout the northern part of Iraq

Pathogenic T cell responses against aquaporin 4

Inflammatory lesions in the central nervous system of patients with neuromyelitis optica are characterized by infiltration of T cells and deposition of aquaporin-4-specific antibodies and complement on astrocytes at the glia limitans. Although the contribution of aquaporin-4-specific autoantibodies to the disease process has been recently elucidated, a potential role of aquaporin-4-specific T cells in lesion formation is unresolved. To address this issue, we raised aquaporin-4-specific T cell lines in Lewis rats and characterized their pathogenic potential in the presence and absence of aquaporin-4-specific autoantibodies of neuromyelitis optica patients. We show that aquaporin-4-specific T cells induce brain inflammation with particular targeting of the astrocytic glia limitans and permit the entry of pathogenic anti-aquaporin-4-specific antibodies to induce NMO-like lesions in spinal cord and brain. In addition, transfer of aquaporin-4-specific T cells provoked mild (subclinical) myositis and interstitial nephritis. We further show that the expression of the conformational epitope, recognized by NMO patient-derived aquaporin-4-specific antibodies is induced in kidney cells by the pro-inflammatory cytokine gamma-interferon. Our data provide further support for the view that NMO lesions may be induced by a complex interplay of T cell mediated and humoral immune responses against aquaporin-4

The pre-history of health psychology in the UK: From natural science and psychoanalysis to social science, social cognition and beyond

Health psychology formally came of age in the United Kingdom in the 1980s, but it was prefigured by much discussion about challenges to the dominance of biomedicine in healthcare and debates. This articles focuses on what could be termed the pre-history of health psychology in the UK. This was the period in the earlier 20th century when psychological approaches were dominated by psychoanalysis which was followed by behaviourism and then cognitivism. Review of this pre-history provides the backdrop for the rise of health psychology in the UK and also reveals the tensions between the different theoretical perspectives

Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle

Neuronal activity within the central nervous system (CNS) strictly depends on homeostasis and therefore does not tolerate uncontrolled entry of blood components. It has been generally believed that under normal conditions, the endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid barrier (BCSFB) prevent immune cell entry into the CNS. This view has recently changed when it was realized that activated T cells are able to breach the BBB and the BCSFB to perform immune surveillance of the CNS. Here we propose that the immune privilege of the CNS is established by the specific morphological architecture of its borders resembling that of a medieval castle. The BBB and the BCSFB serve as the outer walls of the castle, which can be breached by activated immune cells serving as messengers for outside dangers. Having crossed the BBB or the BCSFB they reach the castle moat, namely the cerebrospinal fluid (CSF)-drained leptomeningeal and perivascular spaces of the CNS. Next to the CNS parenchyma, the castle moat is bordered by a second wall, the glia limitans, composed of astrocytic foot processes and a parenchymal basement membrane. Inside the castle, that is the CNS parenchyma proper, the royal family of sensitive neurons resides with their servants, the glial cells. Within the CSF-drained castle moat, macrophages serve as guards collecting all the information from within the castle, which they can present to the immune-surveying T cells. If in their communication with the castle moat macrophages, T cells recognize their specific antigen and see that the royal family is in danger, they will become activated and by opening doors in the outer wall of the castle allow the entry of additional immune cells into the castle moat. From there, immune cells may breach the inner castle wall with the aim to defend the castle inhabitants by eliminating the invading enemy. If the immune response by unknown mechanisms turns against self, that is the castle inhabitants, this may allow for continuous entry of immune cells into the castle and lead to the death of the castle inhabitants, and finally members of the royal family, the neurons. This review will summarize the molecular traffic signals known to allow immune cells to breach the outer and inner walls of the CNS castle moat and will highlight the importance of the CSF-drained castle moat in maintaining immune surveillance and in mounting immune responses in the CNS