Contrast agents for molecular photoacoustic imaging.

Photoacoustic imaging (PAI) is an emerging tool that bridges the traditional depth limits of ballistic optical imaging and the resolution limits of diffuse optical imaging. Using the acoustic waves generated in response to the absorption of pulsed laser light, it provides noninvasive images of absorbed optical energy density at depths of several centimeters with a resolution of ∼100 μm. This versatile and scalable imaging modality has now shown potential for molecular imaging, which enables visualization of biological processes with systemically introduced contrast agents. Understanding the relative merits of the vast range of contrast agents available, from small-molecule dyes to gold and carbon nanostructures to liposome encapsulations, is a considerable challenge. Here we critically review the physical, chemical and biochemical characteristics of the existing photoacoustic contrast agents, highlighting key applications and present challenges for molecular PAI.This work was supported by CRUK (Career Establishment Award no. C47594/A16267 to J.W. and S.E.B., Core Funding C14303/A17197 to J.W. and S.E.B.), the European Commission (CIG FP7-PEOPLE- 2013-CIG-630729 to J.W. and S.E.B.), the EPSRC-CRUK Cancer Imaging Centre in Cambridge and Manchester (C197/A16465 to J.W. and S.E.B.), King’s College London and University College London Comprehensive Cancer Imaging Centre Cancer Research UK & Engineering and Physical Sciences Research Council, in association with the Medical Research Council and the Department of Health, UK (P.B.), and the European Union (project FAMOS FP7 ICT, contract 317744 to P.B.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nmeth.392

Amazon River infl uence on nitrogen fi xation in the western tropical North Atlantic

We measured rates of N- and C-fixation with a direct tracer method in regions of the western tropical North Atlantic influenced by the Amazon River plume during the high flow period of 2010 (May–June 2010). We found distinct regional variations in N-fixation activity, with the lowest rates in the plume proper and the highest rates in the plume margins and in offshore waters. A comparison of our N- and C-fixation measurements showed that the relative contribution of N-fixation to total primary production increased from the plume core toward oceanic waters, and that most of the C-fixation in this system was supported by sources of nitrogen other than those derived from biological N-fixation, or diazotrophy. We complemented these rate experiments with measurements of the δ15N of suspended particles (δ15PN), which documented the important and often dominant role of diazotrophs in supplying nitrogen to particulate organic matter in the water column. These coupled measurements revealed that small phytoplankton contributed more new nitrogen to the particulate nitrogen pool than larger phytoplankton. We used a habitat classification method to assess the fac- tors that control diazotrophic activity and contribution to the suspended particle pool, both of which increased from the plume toward oceanic waters. Our findings provide an important constraint on the role of the Amazon plume in creating distinct niches and roles for diazotrophs in the nutrient and carbon budgets of the western tropical North Atlantic

Peripheral halo-functionalization in [Cu(N^N)(P^P)]+ emitters: influence on the performances of light-emitting electrochemical cells

A series of heteroleptic [Cu(N^N)(P^P)][PF6] complexes is described in which P^P = bis(2-(diphenylphosphino)phenyl)ether (POP) or 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos) and N^N = 4,4′-diphenyl-6,6′-dimethyl-2,2′-bipyridine substituted in the 4-position of the phenyl groups with atom X (N^N = 1 has X = F, 2 has X = Cl, 3 has X = Br, 4 has X = I; the benchmark N^N ligand with X = H is 5). These complexes have been characterized by multinuclear NMR spectroscopy, mass spectrometry, elemental analyses and cyclic voltammetry; representative single crystal structures are also reported. The solution absorption spectra are characterized by high energy bands (arising from ligand-centred transitions) which are red-shifted on going from X = H to X = I, and a broad metal-to-ligand charge transfer band with λmax in the range 387–395 nm. The ten complexes are yellow emitters in solution and yellow or yellow-orange emitters in the solid-state. For a given N^N ligand, the solution photoluminescence (PL) spectra show no significant change on going from [Cu(N^N)(POP)]+ to [Cu(N^N)(xantphos)]+; introducing the iodo-functionality into the N^N domain leads to a red-shift in λmaxem compared to the complexes with the benchmark N^N ligand 5. In the solid state, [Cu(1)(POP)][PF6] and [Cu(1)(xantphos)][PF6] (fluoro-substituent) exhibit the highest PL quantum yields (74 and 25%, respectively) with values of τ1/2 = 11.1 and 5.8 μs, respectively. Light-emitting electrochemical cells (LECs) with [Cu(N^N)(P^P)][PF6] complexes in the emissive layer have been tested. Using a block-wave pulsed current driving mode, the best performing device employed [Cu(1)(xantphos)]+ and this showed a maximum luminance (Lummax) of 129 cd m−2 and a device lifetime (t1/2) of 54 h; however, the turn-on time (time to reach Lummax) was 4.1 h. Trends in performance data reveal that the introduction of fluoro-groups is beneficial, but that the incorporation of heavier halo-substituents leads to poor devices, probably due to a detrimental effect on charge transport; LECs with the iodo-functionalized N^N ligand 4 failed to show any electroluminescence after 50 h

Effects of short-chain fatty acids on intestinal function in an enteroid model of hypoxia

The healthy GI tract is physiologically hypoxic, but this may be perturbed by certain acute and chronic stressors that reduce oxygen availability systemically. Short-chain fatty acids have been shown to have beneficial effects on intestinal barrier function and inflammation. Therefore, our objective was to see whether short-chain fatty acids (SCFA) would improve GI barrier function, reduce production of pro-inflammatory cytokines, and increase the expression of genes regulating GI barrier function in enteroids exposed to hypoxia. Human duodenal enteroid monolayers were placed under hypoxia (1.0% O2) for 72 h with either 24, or 48 h pre-treatment with a high acetate ratio of SCFA’s or high butyrate ratio or placed under hypoxia concurrently. Transepithelial electrical resistance (TEER) increased with SCFA pre-treatment, especially 48 h of pre-treatment and this was maintained through the first 48 h of hypoxia while cells saw barrier function dramatically decrease by 72 h of hypoxia exposure. Inflammatory protein secretion largely decreased with exposure to hypoxia, regardless of SCFA pre-treatment. Gene expression of several genes related to barrier function were decreased with exposure to hypoxia, and with concurrent and 24 h SCFA pre-treatment. However, 48 h SCFA pre-treatment with a high butyrate ratio increased expression of several metabolic and differentiation related genes. Overall, pre-treatment or concurrent treatment with SCFA mixtures were not able to overcome the negative impacts of hypoxia on intestinal function and cells ultimately still cannot be sustained under hypoxia for 72 h. However, 48 h pre-treatment maintains TEER for up to 48 h of hypoxia while upregulating several metabolic genes

External and internal grouping characteristics of juvenile walleye pollock in the Eastern Bering Sea

Size and shape patterns of fish groups are collective outcomes of interactions among members. Consequently, group-level patterns are often affected when any member responds to changes in their internal state, external state, and environment. To determine how groups of fish respond to components of their physical and ecological environment, and whether the response is influenced by a component of their external state (i.e., fish age), we used a multibeam system to collect three-dimensional grouping characteristics of 5 age categories of juvenile walleye pollock (age 1, age 2, age 3, mixed ages 1 and 2, and mixed ages 2 and 3) across the eastern Bering Sea shelf over two consecutive years (2009–2010). Grouping data were expressed as metrics that described group size (length, height), shape (roundness, spread), internal structure (density, internal heterogeneity), and position (depth, distance above bottom). Physical data (water temperature measurements) were collected with temperature-depth probes, and ecological data (densities of predators and prey − adult walleye pollock and euphausiids, respectively) were collected with an EK60 vertical echosounder. Juvenile pollock maintained a relatively constant shape, size-dependent density (number fish/mean body length3), and internal horizontal heterogeneity among age categories and in the presence of predators and prey. There were changes to group structure in the face of local physical forcing. Groups tended to move towards the seafloor when bottom waters became warmer, and groups became vertically shorter, denser, and had more variation in horizontal internal density as group depth increased. These results are explored in relation to the value and limitations of using multibeam data to describe how external and internal group structure map onto environmental influences

Nitrogen sources and net growth efficiency of zooplankton in three Amazon River plume food webs

The plasticity of nitrogen specific net growth efficiency (NGE) in marine mesozooplankton is currently unresolved, with discordant lines of evidence suggesting that NGE is constant, or that it varies with nitrogen source, food availability, and food quality in marine ecosystems. Specifically, the fate of nitrogen from nitrogen fixation is poorly known. We use 15N : 14N ratios in plankton in combination with hydrological data, nutrient profiles, and nitrogen fixation rate measurements to investigate the relationship between new nitrogen sources and the nitrogen specific NGE in three plankton communities along the outer Amazon River plume. The NGE of small (200–500 μm) mesozooplankton was estimated from the δ 15N differences between particulate nitrogen and zooplankton using an open system Rayleigh fractionation model. The transfer efficiency of nitrogen among larger (\u3e 500 μm) mesozooplankton was estimated from the change in δ 15N as a function of zooplankton size. The Amazon River was not a significant source of bioavailable nitrogen anywhere in our study region, and subsurface nitrate was the primary new nitrogen source for the outer shelf community, which was dominated by diatoms. N2 fixation was the principal new nitrogen source at sites of high diatom diazotroph association abundance and at oceanic sites dominated by Trichodesmium spp. and Synechococcus spp. Although we found clear spatial differences in food quantity, food quality, and diazotroph inputs into mesozooplankton, our data show no significant differences in mesozooplankton nitrogen transfer efficiency and NGE (for latter, mean ± SD: 59 ± 10%) among sites

Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells

Mechanotransduction via yes-associated protein (YAP) is a central mechanism for decision-making in mouse embryonic stem cells (mESCs). Nuclear localization of YAP is tightly connected to pluripotency and increases the cell division rate (CDR). How the geometry of the extracellular environment influences mechanotransduction, thereby YAP localization, and decision-making of single isolated mESCs is largely unknown. To investigate this relation, we produced well-defined 2D and 2.5D microenvironments and monitored CDR and subcellular YAP localization in single mESCs hence excluding cell–cell interactions. By systematically varying size and shape of the 2D and 2.5D substrates we observed that the geometry of the growth environment affects the CDR. Whereas CDR increases with increasing adhesive area in 2D, CDR is highest in small 2.5D micro-wells. Here, mESCs attach to all four walls and exhibit a cross-shaped cell and nuclear morphology. This observation indicates that changes in cell shape are linked to a high CDR. Inhibition of actomyosin activity abrogate these effects. Correspondingly, nuclear YAP localization decreases in inhibitor treated cells, suggesting a relation between cell shape, intracellular forces, and cell division rate. The simplicity of our system guarantees high standardization and reproducibility for monitoring stem cell reactions and allows addressing a variety of fundamental biological questions on a single cell level

Mechanisms of micro-terror? Early career CMS academics’ experiences of ‘targets and terror’ in contemporary business schools

In this article, we apply the concept of ‘targets and terror’, previously used in the healthcare sector, to the audit culture within business schools. We explore to what extent terror, or the inculcation of fear through processes of domination, is identifiable in the micro-level experiences of early career academics. Drawing on an international study of 38 Critical Management Studies early career academics from 15 countries, we develop a theoretical framework combining Bourdieu’s modes of domination and Meyerson and Scully’s Tempered Radicalism, which helps us identify top-down and horizontal processes of micro-terror and bottom-up processes of micro-terrorism, specifically self-terrorisation and counter-terrorisation. In extending the study of ‘targets and terror’ cultures to contemporary business schools, we develop a clearer understanding of how domination plays out in the everyday processes of management and self-management. From Bourdieu’s modes of domination, we discern a dark picture of institutional and interpersonal overt and symbolic violence in the name of target achievement. The Tempered Radicalism lens helps us to understand early career academic challenges that can lead to self-terrorisation but also brings possible ways forward, showing early career academics how to resist mechanisms of micro-terror through their own small acts of counter-terrorisation, providing some hope specifically as the basis for collective resistance

ACE-ASIA - Regional climatic and atmospheric chemical effects of Asian dust and pollution

Although continental-scale plumes of Asian dust and pollution reduce the amount of solar radiation reaching the earth's surface and perturb the chemistry of the atmosphere, our ability to quantify these effects has been limited by a lack of critical observations, particularly of layers above the surface. Comprehensive surface, airborne, shipboard, and satellite measurements of Asian aerosol chemical composition, size, optical properties, and radiative impacts were performed during the Asian Pacific Regional Aerosol Characterization Experiment (ACE-Asia) study. Measurements within a massive Chinese dust storm at numerous widely spaced sampling locations revealed the highly complex structure of the atmosphere, in which layers of dust, urban pollution, and biomass-burning smoke may be transported long distances as distinct entities or mixed together. The data allow a first-time assessment of the regional climatic and atmospheric chemical effects of a continental-scale mixture of dust and pollution. Our results show that radiative flux reductions during such episodes are sufficient to cause regional climate change