Chase over the Nile: The Social Evolution of Riverine Landscape in Urban Egypt

Throughout its history, Cairo evolved as a regional metropolis that sprawls along the banks of the Nile accumulating narratives of evolving social landscape. Overlooking the Nile reflected a privileged social position and place for the urban elite. In spatial terms, the urban bourgeoisie tend to develop living havens in enclaves that are distant from the populace’s everyday life. Ironically, exclusive settlements only attract urban growth further in their direction. This chapter offers an analytical reading of the socio-spatial structure of Cairo following the emergence and decline of a series bourgeoisie quarters along the shores of the Nile. It reports urban narratives based on archival records, documents and investigation of historical texts and travelers’ accounts. This essay argues that cities are essentially social constructs in which hierarchy and connectivity are fundamental aspects of its economic and spatial logic. Through social ambition and desire for upgrade, middle class infiltrate into bourgeoisie havens and sometimes encircle it, seeking better living condition inscribed by social mobility and connectivity to centres of wealth and power. Being both natural barrier and cohesive spine, the Nile helped Cairo to develop successive nucleuses of highly crafted urban experiences that have left their imprints on the contemporary urban scene.

Preproendothelin-1 expression in human mesangial cells: evidence for a p38 mitogen-activated protein kinase/protein kinases- C-dependent mechanism

Endothelin-1 (ET-1) has been implicated in the pathogenesis of renal inflammation. This study investigated the mechanisms underlying the synergistic upregulation of preproET-1 gene expression in human mesangial cells after co-stimulation with thrombin and tumor necrosis factor alpha (TNFalpha). Whereas thrombin induced a moderate upregulation of preproET-1 mRNA, co-stimulation with TNFalpha resulted in a strong and protracted upregulation of this mRNA species. Thrombin+TNFalpha-induced upregulation of preproET-1 expression was found to require p38 mitogen-activated protein kinase and protein kinases C, whereas activation of extracellular signal-regulated kinase, c-Jun-N-terminal kinase, or intracellular Ca(2+) release were not required. Actinomycin D chase experiments suggested that enhanced stability of preproET-1 mRNA did not account for the increase in transcript levels. PreproET-1 promoter analysis demonstrated that the 5'-flanking region of preproET-1 encompassed positive regulatory elements engaged by thrombin. Negative modulation of thrombin-induced activation exerted by the distal 5' portion of preproET-1 promoter (-4.4 kbp to 204 bp) was overcome by co-stimulation with TNFalpha, providing a possible mechanism underlying the synergistic upregulation of preproET-1 expression by these two agonists. In conclusion, human mesangial cell expression of preproET-1 may be increased potently in the presence of two common proinflammatory mediators, thereby providing a potential mechanism for ET-1 production in inflammatory renal disease.

Radical 1,4-aryl transfer in arylcarboxamides leading to phthalimides, biaryls and enantiomerically enriched beta-arylethylamines

5-exo Cyclisation of vinyl-, aryl- and alkyl-radicals onto the aryl group of arylcarboxamides is followed by beta-scission of the resulting spirocyclohexadienyl radicals with ejection of a carbamoyl radical. The fate of this radical depends on the substrate but, in the cases studied, either 5-endo cyclisation or direct reduction follows to give phthalimides, biaryls or beta-arylethylamines.

A record of rapid Holocene climate change preserved in hyrax middens from southwestern Africa

The discovery of sensitive paleoenvironmental proxies contained within fossilized rock hyrax middens from the margin of the central Namib Desert, Africa, is providing unprecedented insight into the region's environmental history. High-resolution stable carbon and nitrogen isotope records spanning 0-11,700 cal (calibrated) yr B. P. indicate phases of relatively humid conditions from 8700-7500, 6900-6700, 5600-4900, and 4200-3500 cal yr B. P., with a period of marked aridity occurring from 3500 until ca. 300 cal yr B. P. Transitions between these phases appear to have occurred very rapidly, often within <200 years. Of particular importance are: (1) the observed relationship between regional aridification and the decline in Northern Hemisphere insolation across the Holocene, and (2) the significance of suborbital scale variations in climate that covary strongly with fluctuations in solar forcing. Together, these elements call for a fundamental reexamination of the role of orbital forcing on tropical African systems, and a reconsideration of what factors drive climate change in the region. The quality and resolution of these data far surpass any other evidence available from the region, and the continued development of this unique archive promises to revolutionize paleoenvironmental studies in southern Africa.

Inhibition of Secretion of Interleukin (IL)-12/IL-23 Family Cytokines by 4-Trifluoromethyl-celecoxib Is Coupled to Degradation via the Endoplasmic Reticulum Stress Protein HERP

Interleukin-12 (IL-12), p80, and IL-23 are structurally related cytokines sharing a p40 subunit. We have recently demonstrated that celecoxib and its COX-2-independent analogue 4-trifluoromethyl-celecoxib (TFM-C) inhibit secretion but not transcription of IL-12 (p35/p40) and p80 (p40/p40). This is associated with a mechanism involving altered cytokine-chaperone interaction in the endoplasmic reticulum (ER). In the present study, we found that celecoxib and TFM-C also block secretion of IL-23 (p40/p19 heterodimers). Given the putative ER-centric mode of these compounds, we performed a comprehensive RTPCR analysis of 23 ER-resident chaperones/foldases and associated co-factors. This revealed that TFM-C induced 1.5-3-fold transcriptional up-regulation of calreticulin, GRP78, GRP94, GRP170, ERp72, ERp57, ERdj4, and ERp29. However, more significantly, a 7-fold up-regulation of homocysteine-inducible ER protein (HERP) was observed. HERP is part of a high molecular mass protein complex involved in ER-associated protein degradation (ERAD). Using co-immunoprecipitation assays, we show that TFM-C induces protein interaction of p80 and IL-23 with HERP. Both HERP siRNA knockdown and HERP overexpression coupled to cycloheximide chase assays revealed that HERP is necessary for degradation of intracellularly retained p80 by TFM-C. Thus, our data suggest that targeting cytokine folding in the ER by small molecule drugs could be therapeutically exploited to alleviate in appropriate inflammation in autoimmune conditions.

Evidence for progressive Holocene aridification in southern Africa recorded in Namibian hyrax middens: Implications for African Monsoon dynamics and the

Presented here are stable nitrogen isotope data from a rock hyrax (Procavia capensis) middens from northwestern Namibia that record a series of rapid aridification events beginning at ca. 3800 cal yr BP, and which mark a progressive decrease in regional humidity across the Holocene. Strong correlations exist between this record and other terrestrial and marine archives from southern Africa, indicating that the observed pattern of climate change is regionally coherent. Combined, these data indicate hemispheric synchrony in tropical African climate change during the Holocene, with similar trends characterising the termination of the 'African Humid Period' (AHP) in both the northern and southern tropics. These findings run counter to the widely accepted model of direct low-latitude insolation forcing, which requires an antiphase relationship to exist between the hemispheres. The combined dataset highlights: 1) the importance of forcing mechanisms influencing the high northern latitudes in effecting low-latitude climate change in Africa, and 2) the potential importance of solar forcing and variations in the Earth's geomagnetic shield in determining both long-term and rapid centennial-scale climate changes, identifying a possible mechanism for the variations marking the AHP termination in both the southern and northern tropics. (C) 2010 University of Washington. Published by Elsevier Inc. All rights reserved.

Isolation of monocytes from human peripheral blood using immuno-affinity expanded-bed adsorption

A novel technique for the separation of monocytes from human peripheral blood preparations has been developed. The technique is based on the use of expanded-bed adsorption and a solid perfluorocarbon derivatized with avidin or streptavidin for the indirect positive or negative capture of cells labeled with biotinylated monoclonal antibodies. The perfluorocarbon support was prepared and characterized and the contactor design and operating conditions, that enable cells to be selectively isolated, were investigated. Experiments consisted of applying an immunolabeled pulse of 1 x 10(8) peripheral blood mononuclear cells (PBMCs), isolated by density gradient centrifugation, directly onto a refrigerated expanded bed. The major cell types remaining were T-lymphocytes, B-lymphocytes, and monocytes. Monocytes could be positively adsorbed, following labeling with anti-CD14 mAb, with a clearance of up to 89% and a depletion factor of 7.6. They could also be

Late glacial interhemispheric climate dynamics revealed in South African hyrax middens

Our ability to identify the timing and extent of past major climate fluctuations is central to understanding changes in the global climate system. Of the events that have occurred in recent geological time, the Younger Dryas (YD, 13-11.5 ka), an abrupt return to near-glacial conditions during the last glacial-interglacial transition (ca. 18-11.5 ka), is one of the most widely reported. While this event is apparent throughout the Northern Hemisphere (Peteet, 1995), evidence for its occurrence in the Southern Hemisphere remains equivocal due to a lack of well-dated terrestrial records. Here we report high-resolution stable carbon and nitrogen isotope records obtained from a rock hyrax midden, revealing the first unequivocal terrestrial manifestation of the YD from the southern African subtropics. These results provide key evidence for the relative influence of the YD, and suggest that a subtropical-temperate transition zone existed along the oceanic Subtropical Front (similar to 41 degrees S) across the Southern Hemisphere, with the Northern Hemisphere exerting a strong influence on all but the higher latitudes of the Southern Hemisphere after the Heinrich Stadial 1 (15 ka).

Rock hyrax middens: A palaeoenvironmental archive for southern African drylands

Like many of the world's subtropical regions, southern Africa is highly sensitive to changes in the earth's climate system, but a dearth of reliable palaeoenvironmental records means that relatively little is known about how regional environments have been affected over centennial to multi-millennial timescales. To a large extent this sensitivity is a function of the position of these regions at the interface between temperate and tropical circulation systems. The resulting seasonality and irregularity of rainfall have limited the development of suitable archives, such as lakes and wetlands, for the preservation of palaeoenvironmental proxies.

This paper reviews and evaluates the value of rock hyrax middens as novel palaeoenvironmental archives in southern Africa. Considered are (1) the contemporary taxonomy, distribution and ecology of hyraxes, (2) the mechanisms of hyrax midden development, their physical and chemical structure, rates of accumulation and age; and (3) the palaeoenvironmental proxies preserved within hyrax middens, including fossil pollen, stable isotopes and biomarkers. The interpretive constraints and opportunities offered by these various midden characteristics are assessed with a view to demonstrating the potential of these deposits, widespread as they are through arid and semi-arid southern Africa, in providing a more detailed and chronologically resolved view of late Quaternary palaeoenvironments across the subcontinent. (C) 2012 Elsevier Ltd. All rights reserved.

Post-Translational Inhibition of IP-10 Secretion in IEC by Probiotic Bacteria: Impact on Chronic Inflammation

Background: Clinical and experimental studies suggest that the probiotic mixture VSL#3 has protective activities in the context of inflammatory bowel disease (IBD). The aim of the study was to reveal bacterial strain-specific molecular mechanisms underlying the anti-inflammatory potential of VSL#3 in intestinal epithelial cells (IEC).

Methodology/Principal Findings: VSL#3 inhibited TNF-induced secretion of the T-cell chemokine interferon-inducible protein (IP-10) in Mode-K cells. Lactobacillus casei (L. casei) cell surface proteins were identified as active anti-inflammatory components of VSL#3. Interestingly, L. casei failed to block TNF-induced IP-10 promoter activity or IP-10 gene transcription at the mRNA expression level but completely inhibited IP-10 protein secretion as well as IP-10-mediated T-cell transmigration. Kinetic studies, pulse-chase experiments and the use of a pharmacological inhibitor for the export machinery (brefeldin A) showed that L. casei did not impair initial IP-10 production but decreased intracellular IP-10 protein stability as a result of blocked IP-10 secretion. Although L. casei induced IP-10 ubiquitination, the inhibition of proteasomal or lysosomal degradation did not prevent the loss of intracellular IP-10. Most important for the mechanistic understanding, the inhibition of vesicular trafficking by 3-methyladenine (3-MA) inhibited IP-10 but not IL-6 expression, mimicking the inhibitory effects of L. casei. These findings suggest that L. casei impairs vesicular pathways important for the secretion of IP-10, followed by subsequent degradation of the proinflammatory chemokine. Feeding studies in TNF Delta ARE and IL-10(-/-) mice revealed a compartimentalized protection of VSL#3 on the development of cecal but not on ileal or colonic inflammation. Consistent with reduced tissue pathology in IL-10(-/-) mice, IP-10 protein expression was reduced in primary epithelial cells.

Conclusions/Significance: We demonstrate segment specific effects of probiotic intervention that correlate with reduced IP-10 protein expression in the native epithelium. Furthermore, we revealed post-translational degradation of IP-10 protein in IEC to be the molecular mechanism underlying the anti-inflammatory effect.

Cheetahs, Acinonyx jubatus, balance turn capacity with pace when chasing prey

Predator–prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world's fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s-1 and accelerated up to 7.5 m s-2 with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5–8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival.

A high resolution 15,600-year pollen and microcharcoal record from the Cederberg Mountains, South Africa

The Cederberg Mountains (Western Cape Province, South Africa) are located within the Fynbos Biome, which exhibits some of the highest levels of species richness and endemism in the world. The region's post-glacial vegetation history, however, remains largely unknown. Presented here are high resolution pollen and microcharcoal records spanning the last 15,600 years obtained from the De Rif rock hyrax midden from the Driehoek Valley of the central Cederberg. In this region, previous pollen studies have shown muted variability in vegetation community composition during periods of globally marked climatic variability (e.g. the last glacial-interglacial transition). In our record, however, significant changes in vegetation composition are apparent. Most notably, they indicate a shift from ericaceous/restioid fynbos (present from 15,600 to 13,300 cal yr BP) to a brief, but prominent, development of proteoid fynbos at the beginning of the Holocene around 11,200 cal yr BP. This vegetation shift is associated with increased moisture at the site, and coincides with reduced fire frequency as indicated by the microcharcoal record. At 10,400 cal yr BP, there is a marked reduction in Protea-type pollen, which is replaced by thicket, characterised by Dodonaea, which became the dominant arboreal pollen type. This shift was likely the result of a long relatively fire-free period coupled with warmer and wetter climates spanning much of the early Holocene. A brief but marked decrease in water availability around 8500-8000 cal yr BP resulted in the strong decrease of Dodonaea pollen. The vegetation of the mid- to late Holocene is characterised by the increased occurrence of Asteraceae and succulent taxa, suggesting substantially drier conditions. These data give unprecedented insight into the vegetation dynamics across a period of substantial, rapid climate change, and while they confirm the presence of fynbos elements throughout the last 15,600 years, the results highlight significant fluctuations in the vegetation that were triggered by changes in both climate and fire regimes. (C) 2013 Elsevier B.V. All rights reserved.

Influence of tropical easterlies in southern Africa's winter rainfall zone during the Holocene

South Africa's southwestern Cape occupies a critical transition zone between Southern Hemisphere temperate (winter) and tropical (summer) moisture-bearing systems. In the recent geological past, it has been proposed that the relative influence of these systems may have changed substantially, but little reliable evidence regarding regional hydroclimates and rainfall seasonality exists to refine or substantiate the understanding of long-term dynamics. In this paper we present a mid-to late Holocene multi-proxy record of environmental change from a rock hyrax midden from Katbakkies Pass, located along the modern boundary between the winter and summer rainfall zones. Derived from stable carbon and nitrogen isotopes, fossil pollen and microcharcoal, these data provide a high resolution record of changes in humidity, and insight into changes in rainfall seasonality. Whereas previous work concluded that the site had generally experienced only subtle environmental change during the Holocene, our records indicate that significant, abrupt changes have occurred in the region over the last 7000 years. Contrary to expectations based on the site's location, these data indicate that the primary determinant of changes in humidity is summer rather than winter rainfall variability, and its influence on drought season intensity and/or length. These findings are consistent with independent records of upwelling along the southern and western coasts, which indicate that periods of increased humidity are related to increased tropical easterly flow. This substantially refines our understanding of the nature of temperate and tropical circulation system dynamics in SW Africa, and how changes in their relative dominance have impacted regional environments during the Holocene. 

Evolving southwest African response to abrupt deglacial North Atlantic climate change events

Climate change during the last deglaciation was strongly influenced by the „bipolar seesaw‟, producing antiphase climate responses between the North and South Atlantic. However, mounting evidence demands refinements of this model, with the occurrence of abrupt events in southern low to mid latitudes occurring in-phase with North Atlantic climate. Improved constraints on the north-south phasing and spatial extent of these events are therefore critical to
understanding the mechanisms that propagate abrupt events within the climate system. We present a 19,400 year multi-proxy record of climate change obtained from a rock hyrax midden in southernmost Africa. Arid anomalies in phase with the Younger Dryas and 8.2 ka events are apparent, indicating a clear shift in the influence of the bipolar seesaw, which diminished as the Earth warmed, and was succeeded after ~14.6 ka by the emergence of a dominant interhemispheric atmospheric teleconnection.