227 research outputs found

    Fulayj: a late Sasanian fort on the Arabian coast

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    Archaeological evidence for a Sasanian presence in the ‘Uman region of Eastern Arabia is sparse. Recent excavations at the site of Fulayj in Oman have, however, revealed it to be a Late Sasanian fort, the only securely dated example in Arabia, or indeed on the western shores of the Indian Ocean more generally. AMS dating supports the ceramic chronology proposed for the site, demonstrating occupation until the Islamisation of South-eastern Arabia in the early seventh century AD, and also briefly into the very Early Islamic period. Fulayj fort provides new insights into Sasanian military activities during this crucial period of Arabian history

    Bilad al-Qadim revisited: recent archaeological research at the Al-Khamis Mosque, Ain Abu Zaydan and Abu Anbra, Bahrain

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    This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.In comparison to our understanding of pre-Islamic occupation and land use on Bahrain, that of the Islamic period has remained less well known. In connection with the building of a visitor centre at the Al-Khamis Mosque and the planning of an associated heritage trail, renewed archaeological research has taken place in Bilad al-Qadim, an archaeologically important area of Islamic settlement in the north-east of the main island of Awal. This has involved excavations in the Abu Anbra cemetery, at Ain Abu Zaydan and at the Al-Khamis Mosque. The results of these excavations are reported here and these contribute to our understanding of Islamic settlement on Bahrain by supporting the interpretation that Bilad al-Qadim was the main centre of Islamic settlement in the eleventh–thirteen century AD

    Light-mediated remote control of signaling pathways

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    Cell signaling networks display an extraordinary range of temporal and spatial plasticity. Our programmatic approach focuses on the construction of intracellular probes, including sensors, inhibitors, and functionally unique proteins that can be temporally and spatially controlled by the investigator even after they have entered the cell. We have designed and evaluated protein kinase sensors that furnish a fluorescent readout upon phosphorylation. In addition, since the sensors are inert (i.e. cannot be phosphorylated) until activated by light, they can be carried through the various stages of any given cell-based behavior without being consumed. Using this strategy, we have shown that PKCβ is essential for nuclear envelope breakdown and thus the transition from prophase to metaphase in actively dividing cells. Photoactivatable proteins furnish the means to initiate cellular signaling pathways with a high degree of spatial and temporal control. We have used this approach to demonstrate that cofilin serves as a component of the steering apparatus of the cell. Finally, inhibitors are commonly used to assess the participation of specific enzymes in signaling pathways that control cellular behavior. We have constructed a photo-deactivatable inhibitor, an inhibitory species that can be switched off with light. In the absence of light, the target enzyme is inactive due to the presence of the potent inhibitory molecule. Upon photolysis, the inhibitory molecule is destroyed and enzymatic activity is released

    Dual Wavelength Photoactivation of cAMP- and cGMP-Dependent Protein Kinase Signaling Pathways

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    The spatial and temporal organization of biological systems offers a level of complexity that is challenging to probe with conventional reagents. Photoactivatable (caged) compounds represent one strategy by which spatiotemporal organizational complexities can be addressed. However, since the vast majority of caged species are triggered by UV light, it is not feasible to orthogonally control two or more spatiotemporal elements of the phenomenon under investigation. For example, the cGMP- and cAMP-dependent protein kinases are highly homologous enzymes, separated in time and space, which mediate the phosphorylation of both distinct and common protein substrates. However, current technology is unable to discriminate, in a temporally or spatially selective fashion, between these enzymes and/or the pathways they influence. We describe herein the intracellular triggering of a cGMP-mediated pathway with 360 nm light and the corresponding cAMP-mediated pathway with 440 nm light. Dual wavelength photoactivation was assessed in A10 cells by monitoring the phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a known substrate for both the cAMP- and cGMP-dependent protein kinases. Illumination at 440 nm elicits a cAMP-dependent phosphorylation of VASP at Ser157 whereas 360 nm exposure triggers the phosphorylation of both Ser157 and Ser239. This is the first example of wavelength-distinct activation of two separate nodes of a common signaling pathway

    Light-Mediated Spatial Control via Photolabile Fluorescently Quenched Peptide Cassettes

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    Light-regulatable compounds are finding increasing utility as spatial and temporal probes of biological behavior. An independent measure of successful light-induced structural change is possible when alteration (e.g., activation, deactivation, etc.) of the bioprobe can be directly linked to a fluorescent readout. We have identified a series of photolabile fluorescently quenched cassettes that display extraordinarily large fluorescence enhancements upon photolysis. A pair of cassettes has been inserted into mitochondrial localization sequences to assess an organelle-targeted light-mediated release strategy for controlling biological activity. The peptide constructs are readily absorbed by mitochondria and subsequently can be cleaved in a light-dependent fashion as assessed by the predicted changes in absorbance and fluorescence

    Size-dependent increase in RNA Polymerase II initiation rates mediates gene expression scaling with cell size

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    Cell size varies during the cell cycle and in response to external stimuli. This requires the tight coordination, or “scaling”, of mRNA and protein quantities with the cell volume in order to maintain biomolecules concentrations and cell density. Evidence in cell populations and single cells indicates that scaling relies on the coordination of mRNA transcription rates with cell size. Here we use a combination of single-molecule fluorescence in situ hybridisation (smFISH), time-lapse microscopy and mathematical modelling in single fission yeast cells to uncover the precise molecular mechanisms that control transcription rates scaling with cell size. Linear scaling of mRNA quantities is apparent in single fission yeast cells during a normal cell cycle. Transcription rates of both constitutive and regulated genes scale with cell size without evidence for transcriptional bursting. Modelling and experimental data indicate that scaling relies on the coordination of RNAPII transcription initiation rates with cell size and that RNAPII is a limiting factor. We show using real-time quantitative imaging that size increase is accompanied by a rapid concentration independent recruitment of RNAPII onto chromatin. Finally, we find that in multinucleated cells, scaling is set at the level of single nuclei and not the entire cell, making the nucleus the transcriptional scaling unit. Integrating our observations in a mechanistic model of RNAPII mediated transcription, we propose that scaling of gene expression with cell size is the consequence of competition between genes for limiting RNAPII

    Organic Aerosol source apportionment in London 2013 with ME-2:Exploring the solution space with annual and seasonal analysis

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    The multilinear engine (ME-2) factorization tool is being widely used following the recent development of the Source Finder (SoFi) interface at the Paul Scherrer Institute. However, the success of this tool, when using the <i>a</i> value approach, largely depends on the inputs (i.e. target profiles) applied as well as the experience of the user. A strategy to explore the solution space is proposed, in which the solution that best describes the organic aerosol (OA) sources is determined according to the systematic application of predefined statistical tests. This includes trilinear regression, which proves to be a useful tool for comparing different ME-2 solutions. Aerosol Chemical Speciation Monitor (ACSM) measurements were carried out at the urban background site of North Kensington, London from March to December 2013, where for the first time the behaviour of OA sources and their possible environmental implications were studied using an ACSM. Five OA sources were identified: biomass burning OA (BBOA), hydrocarbon-like OA (HOA), cooking OA (COA), semivolatile oxygenated OA (SVOOA) and low-volatility oxygenated OA (LVOOA). ME-2 analysis of the seasonal data sets (spring, summer and autumn) showed a higher variability in the OA sources that was not detected in the combined March–December data set; this variability was explored with the triangle plots <i>f</i>44 : <i>f</i>43 <i>f</i>44 : <i>f</i>60, in which a high variation of SVOOA relative to LVOOA was observed in the <i>f</i>44 : <i>f</i>43 analysis. Hence, it was possible to conclude that, when performing source apportionment to long-term measurements, important information may be lost and this analysis should be done to short periods of time, such as seasonally. Further analysis on the atmospheric implications of these OA sources was carried out, identifying evidence of the possible contribution of heavy-duty diesel vehicles to air pollution during weekdays compared to those fuelled by petrol
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