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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
Genomic NGFB variation and multiple sclerosis in a case control study
<p>Abstract</p> <p>Background</p> <p>Nerve growth factor β (NGFB) is involved in cell proliferation and survival, and it is a mediator of the immune response. ProNGF, the precursor protein of NGFB, has been shown to induce cell death via interaction with the p75 neurotrophin receptor. In addition, this neurotrophin is differentially expressed in males and females. Hence NGFB is a good candidate to influence the course of multiple sclerosis (MS), much like in the murine model of experimental autoimmune encephalomyelitis (EAE).</p> <p>Methods</p> <p>Ten single nucleotide polymorphisms (SNPs) were genotyped in the <it>NGFB </it>gene in up to 1120 unrelated MS patients and 869 controls. Expression analyses were performed for selected MS patients in order to elucidate the possible functional relevance of the SNPs.</p> <p>Results</p> <p>Significant association of NGFB variations with MS is evident for two SNPs. <it>NGFB </it>mRNA seems to be expressed in sex- and disease progression-related manner in peripheral blood mononuclear cells.</p> <p>Conclusion</p> <p>NGFB variation and expression levels appear as modulating factors in the development of MS.</p
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
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
Suppression of experimental autoimmune encephalomyelitis by interleukin-10 transduced neural stem/progenitor cells
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
Microglial activation and chronic neurodegeneration
Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurode-generative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including tumor necrosis factor-α, nitric oxide, interleukin-1β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (e.g., lipopolysaccharide or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss with time. Although the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s disease. We review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype
Neuronal Chemokines: Versatile Messengers In Central Nervous System Cell Interaction
Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS), chemokines are generally found under both physiological and pathological conditions. Whereas many reports describe chemokine expression in astrocytes and microglia and their role in the migration of leukocytes into the CNS, only few studies describe chemokine expression in neurons. Nevertheless, the expression of neuronal chemokines and the corresponding chemokine receptors in CNS cells under physiological and pathological conditions indicates that neuronal chemokines contribute to CNS cell interaction. In this study, we review recent studies describing neuronal chemokine expression and discuss potential roles of neuronal chemokines in neuron–astrocyte, neuron–microglia, and neuron–neuron interaction
Suppression of Her2/neu expression through ILK inhibition is regulated by a pathway involving TWIST and YB-1
In a previous study it was found that the therapeutic effects of QLT0267, a small molecule inhibitor of integrin-linked kinase (ILK), were influenced by Her2/neu expression. To understand how inhibition or silencing of ILK influences Her2/neu expression, Her2/neu signaling was evaluated in six Her2/neu-positive breast cancer cell lines (LCC6Her2, MCF7Her2, SKBR3, BT474, JIMT-1 and KPL-4). Treatment with QLT0267 engendered suppression (32–87%) of total Her2/neu protein in these cells. Suppression of Her2/neu was also observed following small interfering RNA-mediated silencing of ILK expression. Time course studies suggest that ILK inhibition or silencing caused transient decreases in P-AKTser473, which were not temporally related to Her2/neu downregulation. Attenuation of ILK activity or expression was, however, associated with decreases in YB-1 (Y-box binding protein-1) protein and transcript levels. YB-1 is a known transcriptional regulator of Her2/neu expression, and in this study it is demonstrated that inhibition of ILK activity using QLT0267 decreased YB-1 promoter activity by 50.6%. ILK inhibition was associated with changes in YB-1 localization, as reflected by localization of cytoplasmic YB-1 into stress granules. ILK inhibition also suppressed TWIST (a regulator of YB-1 expression) protein expression. To confirm the role of ILK on YB-1 and TWIST, cells were engineered to overexpress ILK. This was associated with a fourfold increase in the level of YB-1 in the nucleus, and a 2- and 1.5-fold increase in TWIST and Her2/neu protein levels, respectively. Taken together, these data indicate that ILK regulates the expression of Her2/neu through TWIST and YB-1, lending support to the use of ILK inhibitors in the treatment of aggressive Her2/neu-positive tumors
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